9lwf: Difference between revisions

Latest revision as of 08:22, 13 August 2025

Cryo-EM structure of dual sensor bound GATOR2 complex

Structural highlights

9lwf is a 20 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.41Å
Ligands:	ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

MIOS_HUMAN As a component of the GATOR2 complex, functions as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway (PubMed:23723238, PubMed:26586190, PubMed:27487210, PubMed:35831510, PubMed:36528027). The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex (PubMed:23723238, PubMed:26586190, PubMed:27487210, PubMed:35831510, PubMed:36528027). GATOR2 probably acts as an E3 ubiquitin-protein ligase toward GATOR1 (PubMed:36528027). In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation (PubMed:36528027). In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex (PubMed:25263562, PubMed:25457612, PubMed:26586190, PubMed:27487210). Within the GATOR2 complex, MIOS is required to prevent autoubiquitination of WDR24, the catalytic subunit of the complex (PubMed:35831510). The GATOR2 complex is required for brain myelination (By similarity).[UniProtKB:Q8VE19]^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7]

References

↑ Bar-Peled L, Chantranupong L, Cherniack AD, Chen WW, Ottina KA, Grabiner BC, Spear ED, Carter SL, Meyerson M, Sabatini DM. A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science. 2013 May 31;340(6136):1100-6. doi: 10.1126/science.1232044. PMID:23723238 doi:https://dx.doi.org/10.1126/science.1232044
↑ Chantranupong L, Wolfson RL, Orozco JM, Saxton RA, Scaria SM, Bar-Peled L, Spooner E, Isasa M, Gygi SP, Sabatini DM. The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. Cell Rep. 2014 Oct 9;9(1):1-8. PMID:25263562 doi:10.1016/j.celrep.2014.09.014
↑ Parmigiani A, Nourbakhsh A, Ding B, Wang W, Kim YC, Akopiants K, Guan KL, Karin M, Budanov AV. Sestrins inhibit mTORC1 kinase activation through the GATOR complex. Cell Rep. 2014 Nov 20;9(4):1281-91. doi: 10.1016/j.celrep.2014.10.019. PMID:25457612 doi:https://dx.doi.org/10.1016/j.celrep.2014.10.019
↑ Saxton RA, Knockenhauer KE, Wolfson RL, Chantranupong L, Pacold ME, Wang T, Schwartz TU, Sabatini DM. Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway. Science. 2015 Nov 19. pii: aad2087. PMID:26586190 doi:https://dx.doi.org/10.1126/science.aad2087
↑ Saxton RA, Chantranupong L, Knockenhauer KE, Schwartz TU, Sabatini DM. Mechanism of arginine sensing by CASTOR1 upstream of mTORC1. Nature. 2016 Aug 11;536(7615):229-33. PMID:27487210 doi:https://dx.doi.org/10.1038/nature19079
↑ Valenstein ML, Rogala KB, Lalgudi PV, Brignole EJ, Gu X, Saxton RA, Chantranupong L, Kolibius J, Quast JP, Sabatini DM. Structure of the nutrient-sensing hub GATOR2. Nature. 2022 Jul;607(7919):610-616. doi: 10.1038/s41586-022-04939-z. Epub 2022, Jul 13. PMID:35831510 doi:https://dx.doi.org/10.1038/s41586-022-04939-z
↑ Jiang C, Dai X, He S, Zhou H, Fang L, Guo J, Liu S, Zhang T, Pan W, Yu H, Fu T, Li D, Inuzuka H, Wang P, Xiao J, Wei W. Ring domains are essential for GATOR2-dependent mTORC1 activation. Mol Cell. 2023 Jan 5;83(1):74-89.e9. PMID:36528027 doi:10.1016/j.molcel.2022.11.021

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OCA

[1] Bar-Peled L, Chantranupong L, Cherniack AD, Chen WW, Ottina KA, Grabiner BC, Spear ED, Carter SL, Meyerson M, Sabatini DM. A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science. 2013 May 31;340(6136):1100-6. doi: 10.1126/science.1232044. PMID:23723238 doi:https://dx.doi.org/10.1126/science.1232044

[2] Chantranupong L, Wolfson RL, Orozco JM, Saxton RA, Scaria SM, Bar-Peled L, Spooner E, Isasa M, Gygi SP, Sabatini DM. The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. Cell Rep. 2014 Oct 9;9(1):1-8. PMID:25263562 doi:10.1016/j.celrep.2014.09.014

[3] Parmigiani A, Nourbakhsh A, Ding B, Wang W, Kim YC, Akopiants K, Guan KL, Karin M, Budanov AV. Sestrins inhibit mTORC1 kinase activation through the GATOR complex. Cell Rep. 2014 Nov 20;9(4):1281-91. doi: 10.1016/j.celrep.2014.10.019. PMID:25457612 doi:https://dx.doi.org/10.1016/j.celrep.2014.10.019

[4] Saxton RA, Knockenhauer KE, Wolfson RL, Chantranupong L, Pacold ME, Wang T, Schwartz TU, Sabatini DM. Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway. Science. 2015 Nov 19. pii: aad2087. PMID:26586190 doi:https://dx.doi.org/10.1126/science.aad2087

[5] Saxton RA, Chantranupong L, Knockenhauer KE, Schwartz TU, Sabatini DM. Mechanism of arginine sensing by CASTOR1 upstream of mTORC1. Nature. 2016 Aug 11;536(7615):229-33. PMID:27487210 doi:https://dx.doi.org/10.1038/nature19079

[6] Valenstein ML, Rogala KB, Lalgudi PV, Brignole EJ, Gu X, Saxton RA, Chantranupong L, Kolibius J, Quast JP, Sabatini DM. Structure of the nutrient-sensing hub GATOR2. Nature. 2022 Jul;607(7919):610-616. doi: 10.1038/s41586-022-04939-z. Epub 2022, Jul 13. PMID:35831510 doi:https://dx.doi.org/10.1038/s41586-022-04939-z

[7] Jiang C, Dai X, He S, Zhou H, Fang L, Guo J, Liu S, Zhang T, Pan W, Yu H, Fu T, Li D, Inuzuka H, Wang P, Xiao J, Wei W. Ring domains are essential for GATOR2-dependent mTORC1 activation. Mol Cell. 2023 Jan 5;83(1):74-89.e9. PMID:36528027 doi:10.1016/j.molcel.2022.11.021

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9lwf is ON HOLD  until Paper Publication
+==Cryo-EM structure of dual sensor bound GATOR2 complex==
+<StructureSection load='9lwf' size='340' side='right'caption='[[9lwf]], [[Resolution|resolution]] 3.41&Aring;' scene=''>
-Authors:
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9lwf]] is a 20 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=9LWF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9LWF FirstGlance]. <br>
-Description:
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.41&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=9lwf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9lwf OCA], [https://pdbe.org/9lwf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9lwf RCSB], [https://www.ebi.ac.uk/pdbsum/9lwf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9lwf ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/MIOS_HUMAN MIOS_HUMAN] As a component of the GATOR2 complex, functions as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway (PubMed:23723238, PubMed:26586190, PubMed:27487210, PubMed:35831510, PubMed:36528027). The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex (PubMed:23723238, PubMed:26586190, PubMed:27487210, PubMed:35831510, PubMed:36528027). GATOR2 probably acts as an E3 ubiquitin-protein ligase toward GATOR1 (PubMed:36528027). In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation (PubMed:36528027). In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex (PubMed:25263562, PubMed:25457612, PubMed:26586190, PubMed:27487210). Within the GATOR2 complex, MIOS is required to prevent autoubiquitination of WDR24, the catalytic subunit of the complex (PubMed:35831510). The GATOR2 complex is required for brain myelination (By similarity).[UniProtKB:Q8VE19]<ref>PMID:23723238</ref> <ref>PMID:25263562</ref> <ref>PMID:25457612</ref> <ref>PMID:26586190</ref> <ref>PMID:27487210</ref> <ref>PMID:35831510</ref> <ref>PMID:36528027</ref>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Su M-Y]]

9lwf: Difference between revisions

Latest revision as of 08:22, 13 August 2025

Cryo-EM structure of dual sensor bound GATOR2 complex

Structural highlights

Function

References

Contents

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