6sb0 - Revision history

OCA at 10:14, 22 May 2024

2024-05-22T10:14:33Z

←Older revision		Revision as of 10:14, 22 May 2024
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	<SX load='6sb0' size='340' side='right' viewer='molstar' caption='[[6sb0]], [[Resolution\|resolution]] 5.50Å' scene=''>		<SX load='6sb0' size='340' side='right' viewer='molstar' caption='[[6sb0]], [[Resolution\|resolution]] 5.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6sb0]] is a 12 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=6SB0 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=6SB0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6sb0]] is a 12 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=6SB0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SB0 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>~~, ~~<scene name='pdbligand=GTP:GUANOSINE-~~5~~-TRIPHOSPHATE'>GTP</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]] 5.5Å</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=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</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]), RRAGA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RRAGC ([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]), AKT1S1, PRAS40 ([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=6sb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sb0 OCA], [https://pdbe.org/6sb0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sb0 RCSB], [https://www.ebi.ac.uk/pdbsum/6sb0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sb0 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=6sb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sb0 OCA], [~~http~~://pdbe.org/6sb0 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6sb0 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6sb0 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6sb0 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[[http://www.uniprot.org/uniprot/AKTS1_HUMAN AKTS1_HUMAN]] Subunit of mTORC1, 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, AKT1S1 negatively regulates mTOR activity in a manner that is dependent on its phosphorylation state and binding to 14-3-3 proteins. Inhibits RHEB-GTP-dependent mTORC1 activation. Substrate for AKT1 phosphorylation, but can also be activated by AKT1-independent mechanisms. May also play a role in nerve growth factor-mediated neuroprotection.<ref>PMID:16174443</ref> <ref>PMID:17277771</ref> <ref>PMID:17386266</ref> [[http://www.uniprot.org/uniprot/RRAGA_HUMAN RRAGA_HUMAN]] Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade. Forms heterodimeric Rag complexes with RRAGC or RRAGD and cycles between an inactive GDP-bound and an active GTP-bound form. In its active form participates in the relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. Involved in the RCC1/Ran-GTPase pathway. May play a direct role in a TNF-alpha signaling pathway leading to induction of cell death. May alternatively act as a cellular target for adenovirus E3-14.7K, an inhibitor of TNF-alpha functions, thereby affecting cell death.<ref>PMID:20381137</ref> <ref>PMID:25936802</ref> <ref>PMID:8995684</ref> <ref>PMID:9394008</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/RRAGC_HUMAN RRAGC_HUMAN]] Guanine nucleotide-binding protein forming heterodimeric Rag complexes required for the amino acid-induced relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. This is a crucial step in the activation of the TOR signaling cascade by amino acids.<ref>PMID:20381137</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>	+	[https://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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
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	==See Also==		==See Also==
-	*[[Raptor\|Raptor]]	+	*[[GTP-binding protein 3D structures\|GTP-binding protein 3D structures]]
		+	*[[Raptor 3D structures\|Raptor 3D structures]]
	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]		*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
Line 28:		Line 28:
	__TOC__		__TOC__
	</SX>		</SX>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Anandapadamanaban, M]]	+	[[Category: Anandapadamanaban M]]
-	[[Category: Berndt, A]]	+	[[Category: Berndt A]]
-	[[Category: Masson~~, G R~~]]	+	[[Category: Masson GR]]
-	[[Category: Perisic, O]]	+	[[Category: Perisic O]]
-	[[Category: Williams~~, R L]]~~	+	[[Category: Williams RL]]
-	~~[[Category: Gtpase domain]]~~	+
-	~~[[Category: Mtorc1 activator]]~~	+
-	~~[[Category: Roadblock domain]]~~	+
-	~~[[Category: Signaling protein]]~~	+
-	~~[[Category: Small gtpase~~]]	+

OCA at 06:05, 11 April 2020

2020-04-11T06:05:08Z

←Older revision		Revision as of 06:05, 11 April 2020
Line 3:		Line 3:
	<SX load='6sb0' size='340' side='right' viewer='molstar' caption='[[6sb0]], [[Resolution\|resolution]] 5.50Å' scene=''>		<SX load='6sb0' size='340' side='right' viewer='molstar' caption='[[6sb0]], [[Resolution\|resolution]] 5.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6sb0]] is a 12 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=6SB0 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6SB0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6sb0]] is a 12 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=6SB0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6SB0 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</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]), RRAGA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RRAGC ([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]), AKT1S1, PRAS40 ([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]), RRAGA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RRAGC ([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]), AKT1S1, PRAS40 ([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'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6sb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sb0 OCA], [http://pdbe.org/6sb0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sb0 RCSB], [http://www.ebi.ac.uk/pdbsum/6sb0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sb0 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=6sb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sb0 OCA], [http://pdbe.org/6sb0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sb0 RCSB], [http://www.ebi.ac.uk/pdbsum/6sb0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sb0 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==

OCA at 00:44, 7 March 2020

2020-03-07T00:44:49Z

←Older revision		Revision as of 00:44, 7 March 2020
Line 1:		Line 1:

	==cryo-EM structure of mTORC1 bound to PRAS40-fused active RagA/C GTPases==		==cryo-EM structure of mTORC1 bound to PRAS40-fused active RagA/C GTPases==
-	<~~StructureSection~~ load='6sb0' size='340' side='right'caption='[[6sb0]], [[Resolution\|resolution]] 5.50Å' scene=''>	+	<SX load='6sb0' size='340' side='right' viewer='molstar' caption='[[6sb0]], [[Resolution\|resolution]] 5.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[6sb0]] is a 12 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=6SB0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SB0 FirstGlance]. <br>		<table><tr><td colspan='2'>[[6sb0]] is a 12 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=6SB0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SB0 FirstGlance]. <br>
Line 20:		Line 20:
	</div>		</div>
	<div class="pdbe-citations 6sb0" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 6sb0" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Raptor\|Raptor]]
		+	*[[Serine/threonine protein kinase 3D structures\|Serine/threonine protein kinase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
-	</~~StructureSection~~>	+	</SX>
	[[Category: Human]]		[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]

OCA at 08:12, 23 October 2019

2019-10-23T08:12:34Z

←Older revision		Revision as of 08:12, 23 October 2019
Line 3:		Line 3:
	<StructureSection load='6sb0' size='340' side='right'caption='[[6sb0]], [[Resolution\|resolution]] 5.50Å' scene=''>		<StructureSection load='6sb0' size='340' side='right'caption='[[6sb0]], [[Resolution\|resolution]] 5.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6sb0]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SB0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SB0 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6sb0]] is a 12 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=6SB0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SB0 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</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]), RRAGA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RRAGC ([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]), AKT1S1, PRAS40 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6sb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sb0 OCA], [http://pdbe.org/6sb0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sb0 RCSB], [http://www.ebi.ac.uk/pdbsum/6sb0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sb0 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=6sb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sb0 OCA], [http://pdbe.org/6sb0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sb0 RCSB], [http://www.ebi.ac.uk/pdbsum/6sb0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sb0 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/AKTS1_HUMAN AKTS1_HUMAN]] Subunit of mTORC1, 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, AKT1S1 negatively regulates mTOR activity in a manner that is dependent on its phosphorylation state and binding to 14-3-3 proteins. Inhibits RHEB-GTP-dependent mTORC1 activation. Substrate for AKT1 phosphorylation, but can also be activated by AKT1-independent mechanisms. May also play a role in nerve growth factor-mediated neuroprotection.<ref>PMID:16174443</ref> <ref>PMID:17277771</ref> <ref>PMID:17386266</ref> [[http://www.uniprot.org/uniprot/RRAGA_HUMAN RRAGA_HUMAN]] Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade. Forms heterodimeric Rag complexes with RRAGC or RRAGD and cycles between an inactive GDP-bound and an active GTP-bound form. In its active form participates in the relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. Involved in the RCC1/Ran-GTPase pathway. May play a direct role in a TNF-alpha signaling pathway leading to induction of cell death. May alternatively act as a cellular target for adenovirus E3-14.7K, an inhibitor of TNF-alpha functions, thereby affecting cell death.<ref>PMID:20381137</ref> <ref>PMID:25936802</ref> <ref>PMID:8995684</ref> <ref>PMID:9394008</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/RRAGC_HUMAN RRAGC_HUMAN]] Guanine nucleotide-binding protein forming heterodimeric Rag complexes required for the amino acid-induced relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. This is a crucial step in the activation of the TOR signaling cascade by amino acids.<ref>PMID:20381137</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/AKTS1_HUMAN AKTS1_HUMAN]] Subunit of mTORC1, 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, AKT1S1 negatively regulates mTOR activity in a manner that is dependent on its phosphorylation state and binding to 14-3-3 proteins. Inhibits RHEB-GTP-dependent mTORC1 activation. Substrate for AKT1 phosphorylation, but can also be activated by AKT1-independent mechanisms. May also play a role in nerve growth factor-mediated neuroprotection.<ref>PMID:16174443</ref> <ref>PMID:17277771</ref> <ref>PMID:17386266</ref> [[http://www.uniprot.org/uniprot/RRAGA_HUMAN RRAGA_HUMAN]] Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade. Forms heterodimeric Rag complexes with RRAGC or RRAGD and cycles between an inactive GDP-bound and an active GTP-bound form. In its active form participates in the relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. Involved in the RCC1/Ran-GTPase pathway. May play a direct role in a TNF-alpha signaling pathway leading to induction of cell death. May alternatively act as a cellular target for adenovirus E3-14.7K, an inhibitor of TNF-alpha functions, thereby affecting cell death.<ref>PMID:20381137</ref> <ref>PMID:25936802</ref> <ref>PMID:8995684</ref> <ref>PMID:9394008</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/RRAGC_HUMAN RRAGC_HUMAN]] Guanine nucleotide-binding protein forming heterodimeric Rag complexes required for the amino acid-induced relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. This is a crucial step in the activation of the TOR signaling cascade by amino acids.<ref>PMID:20381137</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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The Rag guanosine triphosphatases (GTPases) recruit the master kinase mTORC1 to lysosomes to regulate cell growth and proliferation in response to amino acid availability. The nucleotide state of Rag heterodimers is critical for their association with mTORC1. Our cryo-electron microscopy structure of RagA/RagC in complex with mTORC1 shows the details of RagA/RagC binding to the RAPTOR subunit of mTORC1 and explains why only the RagAGTP/RagCGDP nucleotide state binds mTORC1. Previous kinetic studies suggested that GTP binding to one Rag locks the heterodimer to prevent GTP binding to the other. Our crystal structures and dynamics of RagA/RagC show the mechanism for this locking and explain how oncogenic hotspot mutations disrupt this process. In contrast to allosteric activation by RHEB, Rag heterodimer binding does not change mTORC1 conformation and activates mTORC1 by targeting it to lysosomes.
		+
		+	Architecture of human Rag GTPase heterodimers and their complex with mTORC1.,Anandapadamanaban M, Masson GR, Perisic O, Berndt A, Kaufman J, Johnson CM, Santhanam B, Rogala KB, Sabatini DM, Williams RL Science. 2019 Oct 11;366(6462):203-210. doi: 10.1126/science.aax3939. PMID:31601764<ref>PMID:31601764</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6sb0" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Anandapadamanaban, M]]		[[Category: Anandapadamanaban, M]]

OCA at 06:02, 16 October 2019

2019-10-16T06:02:36Z

←Older revision		Revision as of 06:02, 16 October 2019
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6sb0 is ~~ON HOLD~~	+	==cryo-EM structure of mTORC1 bound to PRAS40-fused active RagA/C GTPases==
-		+	<StructureSection load='6sb0' size='340' side='right'caption='[[6sb0]], [[Resolution\|resolution]] 5.50Å' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6sb0]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SB0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6SB0 FirstGlance]. <br>
-	~~Description~~:	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<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='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=6sb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sb0 OCA], [http://pdbe.org/6sb0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6sb0 RCSB], [http://www.ebi.ac.uk/pdbsum/6sb0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6sb0 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/AKTS1_HUMAN AKTS1_HUMAN]] Subunit of mTORC1, 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, AKT1S1 negatively regulates mTOR activity in a manner that is dependent on its phosphorylation state and binding to 14-3-3 proteins. Inhibits RHEB-GTP-dependent mTORC1 activation. Substrate for AKT1 phosphorylation, but can also be activated by AKT1-independent mechanisms. May also play a role in nerve growth factor-mediated neuroprotection.<ref>PMID:16174443</ref> <ref>PMID:17277771</ref> <ref>PMID:17386266</ref> [[http://www.uniprot.org/uniprot/RRAGA_HUMAN RRAGA_HUMAN]] Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade. Forms heterodimeric Rag complexes with RRAGC or RRAGD and cycles between an inactive GDP-bound and an active GTP-bound form. In its active form participates in the relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. Involved in the RCC1/Ran-GTPase pathway. May play a direct role in a TNF-alpha signaling pathway leading to induction of cell death. May alternatively act as a cellular target for adenovirus E3-14.7K, an inhibitor of TNF-alpha functions, thereby affecting cell death.<ref>PMID:20381137</ref> <ref>PMID:25936802</ref> <ref>PMID:8995684</ref> <ref>PMID:9394008</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/RRAGC_HUMAN RRAGC_HUMAN]] Guanine nucleotide-binding protein forming heterodimeric Rag complexes required for the amino acid-induced relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. This is a crucial step in the activation of the TOR signaling cascade by amino acids.<ref>PMID:20381137</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>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Anandapadamanaban, M]]
		+	[[Category: Berndt, A]]
		+	[[Category: Masson, G R]]
		+	[[Category: Perisic, O]]
		+	[[Category: Williams, R L]]
		+	[[Category: Gtpase domain]]
		+	[[Category: Mtorc1 activator]]
		+	[[Category: Roadblock domain]]
		+	[[Category: Signaling protein]]
		+	[[Category: Small gtpase]]

OCA: Protected "6sb0" [edit=sysop:move=sysop]

2019-07-24T04:45:54Z

Protected "6sb0" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:45, 24 July 2019

OCA: New page: '''Unreleased structure''' The entry 6sb0 is ON HOLD Authors: Description: Category: Unreleased Structures

2019-07-24T04:45:53Z

New page: '''Unreleased structure''' The entry 6sb0 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6sb0 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]