5wbh

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (14:10, 4 October 2023) (edit) (undo)
 
Line 1: Line 1:
==Structure of the FRB domain of mTOR bound to a substrate recruitment peptide of S6K1==
==Structure of the FRB domain of mTOR bound to a substrate recruitment peptide of S6K1==
-
<StructureSection load='5wbh' size='340' side='right' caption='[[5wbh]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
+
<StructureSection load='5wbh' size='340' side='right'caption='[[5wbh]], [[Resolution|resolution]] 1.75&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
-
<table><tr><td colspan='2'>[[5wbh]] is a 6 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=5WBH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WBH FirstGlance]. <br>
+
<table><tr><td colspan='2'>[[5wbh]] is a 6 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=5WBH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WBH FirstGlance]. <br>
-
</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]), RPS6KB1, STK14A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.75&#8491;</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'>[https://proteopedia.org/fgij/fg.htm?mol=5wbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wbh OCA], [https://pdbe.org/5wbh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wbh RCSB], [https://www.ebi.ac.uk/pdbsum/5wbh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wbh 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=5wbh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wbh OCA], [http://pdbe.org/5wbh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wbh RCSB], [http://www.ebi.ac.uk/pdbsum/5wbh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wbh ProSAT]</span></td></tr>
+
</table>
</table>
== Function ==
== Function ==
-
[[http://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> [[http://www.uniprot.org/uniprot/KS6B1_HUMAN KS6B1_HUMAN]] Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the preinitiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at 'Thr-412', which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin.<ref>PMID:11500364</ref> <ref>PMID:12801526</ref> <ref>PMID:15341740</ref> <ref>PMID:15071500</ref> <ref>PMID:14673156</ref> <ref>PMID:16286006</ref> <ref>PMID:17052453</ref> <ref>PMID:17053147</ref> <ref>PMID:17936702</ref> <ref>PMID:18952604</ref> <ref>PMID:19085255</ref> <ref>PMID:19720745</ref> <ref>PMID:19995915</ref> <ref>PMID:19935711</ref>
+
[https://www.uniprot.org/uniprot/KS6B1_HUMAN KS6B1_HUMAN] Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mammalian target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the preinitiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function. Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at 'Thr-412', which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B. May be involved in cytoskeletal rearrangement through binding to neurabin.<ref>PMID:11500364</ref> <ref>PMID:12801526</ref> <ref>PMID:15341740</ref> <ref>PMID:15071500</ref> <ref>PMID:14673156</ref> <ref>PMID:16286006</ref> <ref>PMID:17052453</ref> <ref>PMID:17053147</ref> <ref>PMID:17936702</ref> <ref>PMID:18952604</ref> <ref>PMID:19085255</ref> <ref>PMID:19720745</ref> <ref>PMID:19995915</ref> <ref>PMID:19935711</ref>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
Line 19: Line 18:
</div>
</div>
<div class="pdbe-citations 5wbh" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 5wbh" style="background-color:#fffaf0;"></div>
 +
 +
==See Also==
 +
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
-
[[Category: Human]]
+
[[Category: Homo sapiens]]
-
[[Category: Non-specific serine/threonine protein kinase]]
+
[[Category: Large Structures]]
-
[[Category: Pavletich, N P]]
+
[[Category: Pavletich NP]]
-
[[Category: Yang, H]]
+
[[Category: Yang H]]
-
[[Category: Transferase]]
+

Current revision

Structure of the FRB domain of mTOR bound to a substrate recruitment peptide of S6K1

PDB ID 5wbh

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5wbh"
Personal tools