6bcx - Revision history

OCA at 14:21, 13 March 2024

OCA — Wed, 13 Mar 2024 14:21:41 GMT

←Older revision		Revision as of 14:21, 13 March 2024
Line 3:		Line 3:
	<SX load='6bcx' size='340' side='right' viewer='molstar' caption='[[6bcx]], [[Resolution\|resolution]] 3.00Å' scene=''>		<SX load='6bcx' size='340' side='right' viewer='molstar' caption='[[6bcx]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6bcx]] is a 8 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BCX OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6BCX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6bcx]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BCX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6BCX FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>~~, ~~<scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>~~</td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3Å</td></tr>
-	<tr id='~~NonStdRes~~'><td class="sblockLbl"><b>[[~~Non-Standard_Residue~~\|~~NonStd Res~~:]]</b></td><td class="sblockDat"><scene name='pdbligand=~~UNK~~:~~UNKNOWN~~'>~~UNK~~</scene>~~</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MTOR~~, FRAP, FRAP1, FRAP2, RAFT1, RAPT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MLST8, GBL, LST8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RPTOR, KIAA1303, RAPTOR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EIF4EBP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])<~~/td></tr>~~	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6bcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bcx OCA], [https://pdbe.org/6bcx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6bcx RCSB], [https://www.ebi.ac.uk/pdbsum/6bcx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6bcx ProSAT]</span></td></tr>
-	~~<tr id~~='~~activity'><td class~~=~~"sblockLbl"><b>Activity~~:~~</b></td><td class="sblockDat"><span class='plainlinks~~'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </~~span~~></td></tr>	+
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=6bcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bcx OCA], [~~http~~://pdbe.org/6bcx PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6bcx RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6bcx PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6bcx ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/~~4EBP1_HUMAN 4EBP1_HUMAN~~]~~] Regulates eIF4E activity by preventing its assembly into the eIF4F complex. Mediates the regulation of~~ protein ~~translation by hormones, growth factors and other stimuli that signal through the MAP~~ kinase ~~and mTORC1 pathways.<ref>PMID:7935836</ref> [[http://www.uniprot.org/uniprot/RPTOR_HUMAN RPTOR_HUMAN]] Involved in the control~~ of ~~the mammalian target of rapamycin complex 1 (mTORC1) activity which regulates cell~~ growth and survival~~, and autophagy~~ in response to ~~nutrient~~ and ~~hormonal~~ signals~~; functions~~ as ~~a scaffold for recruiting mTORC1 substrates. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation~~ of ~~TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-~~signaling to mTORC1 ~~requires its relocalization to the lysosomes mediated by the Ragulator~~ complex and ~~the Rag GTPases~~. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. ~~mTORC1 phosphorylates~~ EIF4EBP1 and ~~releases it from inhibiting~~ the elongation initiation factor 4E (eiF4E). ~~mTORC1~~ phosphorylates and activates ~~S6K1 at 'Thr-389', which then promotes~~ protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Involved in ciliogenesis.<ref>PMID:12150925</ref> <ref>PMID:12150926</ref> <ref>PMID:23727834</ref> [[http://www.uniprot.org/uniprot/LST8_HUMAN LST8_HUMAN]] Subunit of ~~both mTORC1 and mTORC2~~, ~~which regulates cell growth~~ and ~~survival in response to nutrient and hormonal signals~~. ~~mTORC1 is activated in response to growth factors or amino acids. Growth factor~~-~~stimulated mTORC1 activation involves a AKT1-mediated~~ phosphorylation of ~~TSC1~~-~~TSC2, which leads~~ to ~~the activation of the RHEB GTPase that potently activates the~~ protein ~~kinase activity of mTORC1~~. ~~Amino acid-signaling to~~ mTORC1 ~~requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases~~. ~~Activated~~ mTORC1 ~~up-~~regulates ~~protein synthesis by phosphorylating key regulators~~ of ~~mRNA translation and ribosome synthesis~~. ~~mTORC1~~ phosphorylates ~~EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1~~ at '~~Thr~~-~~389~~', ~~which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, LST8 interacts directly~~ with ~~MTOR~~ and ~~enhances its kinase activity~~. ~~In nutrient-poor conditions, stabilizes~~ the ~~MTOR-RPTOR interaction~~ and ~~favors RPTOR-mediated inhibition~~ of ~~MTOR activity. mTORC2 is also activated by growth factors, but seems to be nutrient~~-~~insensitive~~. mTORC2 ~~seems to function upstream~~ of ~~Rho GTPases to regulate~~ the ~~actin~~ cytoskeleton~~, probably by activating one or more Rho-type guanine nucleotide exchange factors~~. ~~mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays~~ a critical role in ~~AKT1~~ 'Ser-473' ~~phosphorylation~~, ~~which~~ may ~~facilitate~~ the phosphorylation of ~~the~~ activation ~~loop~~ of ~~AKT1 on 'Thr~~-~~308' by PDK1 which is a prerequisite for full activation~~. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422~~'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657~~'.<ref>PMID:12718876</ref> <ref>PMID:~~15467718~~</ref>	+	[https://www.uniprot.org/uniprot/MTOR_HUMAN MTOR_HUMAN] Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B and the inhibitor of translation initiation PDCD4. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 a RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho-type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'.<ref>PMID:12150925</ref> <ref>PMID:12150926</ref> <ref>PMID:12231510</ref> <ref>PMID:12087098</ref> <ref>PMID:14651849</ref> <ref>PMID:12718876</ref> <ref>PMID:15268862</ref> <ref>PMID:15545625</ref> <ref>PMID:15467718</ref> <ref>PMID:15718470</ref> <ref>PMID:18925875</ref> <ref>PMID:18762023</ref> <ref>PMID:18497260</ref> <ref>PMID:20537536</ref> <ref>PMID:20516213</ref> <ref>PMID:21659604</ref>
-	<~~div style="background-color~~:~~#fffaf0;"~~>	+
-	~~== Publication Abstract from PubMed ==~~	+
-	The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by PRAS40. Here we present the 3.0 angstrom cryo-electron microscopy structure of mTORC1 and the 3.4 angstrom structure of activated RHEB-mTORC1. RHEB binds to mTOR distally from the kinase active site, yet causes a global conformational change that allosterically realigns active-site residues, accelerating catalysis. Cancer-associated hyperactivating mutations map to structural elements that maintain the inactive state, and we provide biochemical evidence that they mimic RHEB relieving auto-inhibition. We also present crystal structures of RAPTOR-TOS motif complexes that define the determinants of TOS recognition, of an mTOR FKBP12-rapamycin-binding (FRB) domain-substrate complex that establishes a second substrate-recruitment mechanism, and of a truncated mTOR-PRAS40 complex that reveals PRAS40 inhibits both substrate-recruitment sites. These findings help explain how mTORC1 selects its substrates, how its kinase activity is controlled, and how it is activated by cancer-associated mutations.	+
-		+
-	~~Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40.,Yang H, Jiang X, Li B, Yang HJ, Miller M, Yang A, Dhar A, Pavletich NP Nature. 2017 Dec 13. pii~~: ~~nature25023. doi~~: ~~10.1038~~/~~nature25023.~~ PMID:~~29236692~~<ref>PMID:~~29236692~~</ref>	+
-		+
-	~~From MEDLINE®~~/~~PubMed®, a database of the U.S. National Library of Medicine.~~<br>	+
-	</~~div~~>	+
-	<~~div class="pdbe-citations 6bcx" style="background-color~~:~~#fffaf0;"~~></~~div~~>	+

	==See Also==		==See Also==
-	*[[Raptor\|Raptor]]	+	*[[Raptor 3D structures\|Raptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</SX>		</SX>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Non-specific serine/threonine protein kinase]]~~	+	[[Category: Pavletich NP]]
-	[[Category: Pavletich~~, N P~~]]	+	[[Category: Yang H]]
-	[[Category: Yang, H]]	+
-	~~[[Category: Pikk]]~~	+
-	~~[[Category: Transferase~~]]	+

OCA at 23:20, 10 April 2020

OCA — Fri, 10 Apr 2020 23:20:23 GMT

←Older revision		Revision as of 23:20, 10 April 2020
Line 3:		Line 3:
	<SX load='6bcx' size='340' side='right' viewer='molstar' caption='[[6bcx]], [[Resolution\|resolution]] 3.00Å' scene=''>		<SX load='6bcx' size='340' side='right' viewer='molstar' caption='[[6bcx]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6bcx]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BCX OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6BCX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6bcx]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BCX OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6BCX FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MTOR, FRAP, FRAP1, FRAP2, RAFT1, RAPT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MLST8, GBL, LST8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RPTOR, KIAA1303, RAPTOR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EIF4EBP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MTOR, FRAP, FRAP1, FRAP2, RAFT1, RAPT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MLST8, GBL, LST8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RPTOR, KIAA1303, RAPTOR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EIF4EBP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6bcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bcx OCA], [http://pdbe.org/6bcx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bcx RCSB], [http://www.ebi.ac.uk/pdbsum/6bcx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bcx ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6bcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bcx OCA], [http://pdbe.org/6bcx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bcx RCSB], [http://www.ebi.ac.uk/pdbsum/6bcx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bcx ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 20:30, 6 March 2020

OCA — Fri, 06 Mar 2020 20:30:48 GMT

←Older revision		Revision as of 20:30, 6 March 2020
Line 1:		Line 1:

	==mTORC1 structure refined to 3.0 angstroms==		==mTORC1 structure refined to 3.0 angstroms==
-	<~~StructureSection~~ load='6bcx' size='340' side='right'caption='[[6bcx]], [[Resolution\|resolution]] 3.00Å' scene=''>	+	<SX load='6bcx' size='340' side='right' viewer='molstar' caption='[[6bcx]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6bcx]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BCX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BCX FirstGlance]. <br>		<table><tr><td colspan='2'>[[6bcx]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BCX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BCX FirstGlance]. <br>
Line 27:		Line 27:
	<references/>		<references/>
	__TOC__		__TOC__
-	</~~StructureSection~~>	+	</SX>
	[[Category: Human]]		[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]

OCA at 17:10, 20 November 2019

OCA — Wed, 20 Nov 2019 17:10:45 GMT

←Older revision		Revision as of 17:10, 20 November 2019
Line 1:		Line 1:
-	~~{{Large structure}}~~	+
	==mTORC1 structure refined to 3.0 angstroms==		==mTORC1 structure refined to 3.0 angstroms==
-	<StructureSection load='6bcx' size='340' side='right' caption='[[6bcx]], [[Resolution\|resolution]] 3.00Å' scene=''>	+	<StructureSection load='6bcx' size='340' side='right'caption='[[6bcx]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6bcx]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BCX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BCX FirstGlance]. <br>		<table><tr><td colspan='2'>[[6bcx]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BCX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BCX FirstGlance]. <br>
Line 10:		Line 10:
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bcx OCA], [http://pdbe.org/6bcx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bcx RCSB], [http://www.ebi.ac.uk/pdbsum/6bcx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bcx ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bcx OCA], [http://pdbe.org/6bcx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bcx RCSB], [http://www.ebi.ac.uk/pdbsum/6bcx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bcx ProSAT]</span></td></tr>
	</table>		</table>
-	{{Large structure}}
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/4EBP1_HUMAN 4EBP1_HUMAN]] Regulates eIF4E activity by preventing its assembly into the eIF4F complex. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.<ref>PMID:7935836</ref> [[http://www.uniprot.org/uniprot/RPTOR_HUMAN RPTOR_HUMAN]] Involved in the control of the mammalian target of rapamycin complex 1 (mTORC1) activity which regulates cell growth and survival, and autophagy in response to nutrient and hormonal signals; functions as a scaffold for recruiting mTORC1 substrates. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Involved in ciliogenesis.<ref>PMID:12150925</ref> <ref>PMID:12150926</ref> <ref>PMID:23727834</ref> [[http://www.uniprot.org/uniprot/LST8_HUMAN LST8_HUMAN]] Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity. In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'.<ref>PMID:12718876</ref> <ref>PMID:15467718</ref>		[[http://www.uniprot.org/uniprot/4EBP1_HUMAN 4EBP1_HUMAN]] Regulates eIF4E activity by preventing its assembly into the eIF4F complex. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.<ref>PMID:7935836</ref> [[http://www.uniprot.org/uniprot/RPTOR_HUMAN RPTOR_HUMAN]] Involved in the control of the mammalian target of rapamycin complex 1 (mTORC1) activity which regulates cell growth and survival, and autophagy in response to nutrient and hormonal signals; functions as a scaffold for recruiting mTORC1 substrates. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Involved in ciliogenesis.<ref>PMID:12150925</ref> <ref>PMID:12150926</ref> <ref>PMID:23727834</ref> [[http://www.uniprot.org/uniprot/LST8_HUMAN LST8_HUMAN]] Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity. In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'.<ref>PMID:12718876</ref> <ref>PMID:15467718</ref>
Line 22:		Line 21:
	</div>		</div>
	<div class="pdbe-citations 6bcx" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6bcx" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Raptor\|Raptor]]
	== References ==		== References ==
	<references/>		<references/>
Line 27:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Pavletich, N P]]		[[Category: Pavletich, N P]]

OCA at 09:07, 27 December 2017

OCA — Wed, 27 Dec 2017 09:07:16 GMT

←Older revision		Revision as of 09:07, 27 December 2017
Line 3:		Line 3:
	<StructureSection load='6bcx' size='340' side='right' caption='[[6bcx]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='6bcx' size='340' side='right' caption='[[6bcx]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6bcx]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BCX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BCX FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6bcx]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BCX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BCX FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">MTOR, FRAP, FRAP1, FRAP2, RAFT1, RAPT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MLST8, GBL, LST8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RPTOR, KIAA1303, RAPTOR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EIF4EBP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bcx OCA], [http://pdbe.org/6bcx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bcx RCSB], [http://www.ebi.ac.uk/pdbsum/6bcx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bcx ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bcx OCA], [http://pdbe.org/6bcx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bcx RCSB], [http://www.ebi.ac.uk/pdbsum/6bcx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bcx ProSAT]</span></td></tr>
Line 12:		Line 13:
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/4EBP1_HUMAN 4EBP1_HUMAN]] Regulates eIF4E activity by preventing its assembly into the eIF4F complex. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.<ref>PMID:7935836</ref> [[http://www.uniprot.org/uniprot/RPTOR_HUMAN RPTOR_HUMAN]] Involved in the control of the mammalian target of rapamycin complex 1 (mTORC1) activity which regulates cell growth and survival, and autophagy in response to nutrient and hormonal signals; functions as a scaffold for recruiting mTORC1 substrates. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Involved in ciliogenesis.<ref>PMID:12150925</ref> <ref>PMID:12150926</ref> <ref>PMID:23727834</ref> [[http://www.uniprot.org/uniprot/LST8_HUMAN LST8_HUMAN]] Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity. In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'.<ref>PMID:12718876</ref> <ref>PMID:15467718</ref>		[[http://www.uniprot.org/uniprot/4EBP1_HUMAN 4EBP1_HUMAN]] Regulates eIF4E activity by preventing its assembly into the eIF4F complex. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.<ref>PMID:7935836</ref> [[http://www.uniprot.org/uniprot/RPTOR_HUMAN RPTOR_HUMAN]] Involved in the control of the mammalian target of rapamycin complex 1 (mTORC1) activity which regulates cell growth and survival, and autophagy in response to nutrient and hormonal signals; functions as a scaffold for recruiting mTORC1 substrates. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Involved in ciliogenesis.<ref>PMID:12150925</ref> <ref>PMID:12150926</ref> <ref>PMID:23727834</ref> [[http://www.uniprot.org/uniprot/LST8_HUMAN LST8_HUMAN]] Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity. In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'.<ref>PMID:12718876</ref> <ref>PMID:15467718</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by PRAS40. Here we present the 3.0 angstrom cryo-electron microscopy structure of mTORC1 and the 3.4 angstrom structure of activated RHEB-mTORC1. RHEB binds to mTOR distally from the kinase active site, yet causes a global conformational change that allosterically realigns active-site residues, accelerating catalysis. Cancer-associated hyperactivating mutations map to structural elements that maintain the inactive state, and we provide biochemical evidence that they mimic RHEB relieving auto-inhibition. We also present crystal structures of RAPTOR-TOS motif complexes that define the determinants of TOS recognition, of an mTOR FKBP12-rapamycin-binding (FRB) domain-substrate complex that establishes a second substrate-recruitment mechanism, and of a truncated mTOR-PRAS40 complex that reveals PRAS40 inhibits both substrate-recruitment sites. These findings help explain how mTORC1 selects its substrates, how its kinase activity is controlled, and how it is activated by cancer-associated mutations.
		+
		+	Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40.,Yang H, Jiang X, Li B, Yang HJ, Miller M, Yang A, Dhar A, Pavletich NP Nature. 2017 Dec 13. pii: nature25023. doi: 10.1038/nature25023. PMID:29236692<ref>PMID:29236692</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6bcx" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Non-specific serine/threonine protein kinase]]		[[Category: Non-specific serine/threonine protein kinase]]
	[[Category: Pavletich, N P]]		[[Category: Pavletich, N P]]

OCA at 06:29, 20 December 2017

OCA — Wed, 20 Dec 2017 06:29:09 GMT

←Older revision		Revision as of 06:29, 20 December 2017
Line 1:		Line 1:
-	'''~~Unreleased~~ structure'''	+	{{Large structure}}
-		+	==mTORC1 structure refined to 3.0 angstroms==
-	~~The entry~~ 6bcx is ~~ON HOLD~~	+	<StructureSection load='6bcx' size='340' side='right' caption='[[6bcx]], [[Resolution\|resolution]] 3.00Å' scene=''>
-		+	== Structural highlights ==
-	~~Authors~~:	+	<table><tr><td colspan='2'>[[6bcx]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6BCX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6BCX FirstGlance]. <br>
-		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-	~~Description~~:	+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6bcx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6bcx OCA], [http://pdbe.org/6bcx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6bcx RCSB], [http://www.ebi.ac.uk/pdbsum/6bcx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6bcx ProSAT]</span></td></tr>
		+	</table>
		+	{{Large structure}}
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/4EBP1_HUMAN 4EBP1_HUMAN]] Regulates eIF4E activity by preventing its assembly into the eIF4F complex. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways.<ref>PMID:7935836</ref> [[http://www.uniprot.org/uniprot/RPTOR_HUMAN RPTOR_HUMAN]] Involved in the control of the mammalian target of rapamycin complex 1 (mTORC1) activity which regulates cell growth and survival, and autophagy in response to nutrient and hormonal signals; functions as a scaffold for recruiting mTORC1 substrates. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Involved in ciliogenesis.<ref>PMID:12150925</ref> <ref>PMID:12150926</ref> <ref>PMID:23727834</ref> [[http://www.uniprot.org/uniprot/LST8_HUMAN LST8_HUMAN]] Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity. In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'.<ref>PMID:12718876</ref> <ref>PMID:15467718</ref>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Non-specific serine/threonine protein kinase]]
		+	[[Category: Pavletich, N P]]
		+	[[Category: Yang, H]]
		+	[[Category: Pikk]]
		+	[[Category: Transferase]]

OCA: Protected "6bcx" [edit=sysop:move=sysop]

OCA — Wed, 01 Nov 2017 04:55:48 GMT

Protected "6bcx" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:55, 1 November 2017

OCA: New page: '''Unreleased structure''' The entry 6bcx is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 01 Nov 2017 04:55:46 GMT

New page: '''Unreleased structure''' The entry 6bcx is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6bcx is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]