8ae6

From Proteopedia

(Difference between revisions)

Current revision

Cryo-EM structure of the SEA complex wing (SEACIT)

Structural highlights

8ae6 is a 4 chain structure with sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.7Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

NPR3_YEAST Component of the SEA complex which coats the vacuolar membrane and is involved in intracellular trafficking, autophagy, response to nitrogen starvation, and amino acid biogenesis. Mediates inactivation of the TORC1 complex in response to amino acid starvation. Required for meiotic nuclear division.^[1] ^[2] ^[3]

Publication Abstract from PubMed

The SEA complex (SEAC) is a growth regulator that acts as a GTPase-activating protein (GAP) towards Gtr1, a Rag GTPase that relays nutrient status to the Target of Rapamycin Complex 1 (TORC1) in yeast(1). Functionally, the SEAC has been divided into two subcomplexes: SEACIT, which has GAP activity and inhibits TORC1, and SEACAT, which regulates SEACIT(2). This system is conserved in mammals: the GATOR complex, consisting of GATOR1 (SEACIT) and GATOR2 (SEACAT), transmits amino acid(3) and glucose(4) signals to mTORC1. Despite its importance, the structure of SEAC/GATOR, and thus molecular understanding of its function, is lacking. Here, we solve the cryo-EM structure of the native eight-subunit SEAC. The SEAC has a modular structure in which a COPII-like cage corresponding to SEACAT binds two flexible wings, which correspond to SEACIT. The wings are tethered to the core via Sea3, which forms part of both modules. The GAP mechanism of GATOR1 is conserved in SEACIT, and GAP activity is unaffected by SEACAT in vitro. In vivo, the wings are essential for recruitment of the SEAC to the vacuole, primarily via the EGO complex. Our results indicate that rather than being a direct inhibitor of SEACIT, SEACAT acts as a scaffold for the binding of TORC1 regulators.

Cryo-EM structure of the SEA complex.,Tafur L, Hinterndorfer K, Gabus C, Lamanna C, Bergmann A, Sadian Y, Hamdi F, Kyrilis FL, Kastritis PL, Loewith R Nature. 2022 Nov;611(7935):399-404. doi: 10.1038/s41586-022-05370-0. Epub 2022 , Oct 26. PMID:36289347^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Enyenihi AH, Saunders WS. Large-scale functional genomic analysis of sporulation and meiosis in Saccharomyces cerevisiae. Genetics. 2003 Jan;163(1):47-54. PMID:12586695
↑ Neklesa TK, Davis RW. A genome-wide screen for regulators of TORC1 in response to amino acid starvation reveals a conserved Npr2/3 complex. PLoS Genet. 2009 Jun;5(6):e1000515. PMID:19521502 doi:10.1371/journal.pgen.1000515
↑ Dokudovskaya S, Waharte F, Schlessinger A, Pieper U, Devos DP, Cristea IM, Williams R, Salamero J, Chait BT, Sali A, Field MC, Rout MP, Dargemont C. A conserved coatomer-related complex containing Sec13 and Seh1 dynamically associates with the vacuole in Saccharomyces cerevisiae. Mol Cell Proteomics. 2011 Jun;10(6):M110.006478. doi: 10.1074/mcp.M110.006478., Epub 2011 Mar 31. PMID:21454883 doi:10.1074/mcp.M110.006478
↑ Tafur L, Hinterndorfer K, Gabus C, Lamanna C, Bergmann A, Sadian Y, Hamdi F, Kyrilis FL, Kastritis PL, Loewith R. Cryo-EM structure of the SEA complex. Nature. 2022 Nov;611(7935):399-404. PMID:36289347 doi:10.1038/s41586-022-05370-0

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8ae6"

Categories: Large Structures | Saccharomyces cerevisiae | Loewith R | Tafur L

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 8ae6 is ON HOLD
+==Cryo-EM structure of the SEA complex wing (SEACIT)==
+<StructureSection load='8ae6' size='340' side='right'caption='[[8ae6]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[8ae6]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8AE6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8AE6 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.7&#8491;</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=8ae6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ae6 OCA], [https://pdbe.org/8ae6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ae6 RCSB], [https://www.ebi.ac.uk/pdbsum/8ae6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ae6 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/NPR3_YEAST NPR3_YEAST] Component of the SEA complex which coats the vacuolar membrane and is involved in intracellular trafficking, autophagy, response to nitrogen starvation, and amino acid biogenesis. Mediates inactivation of the TORC1 complex in response to amino acid starvation. Required for meiotic nuclear division.<ref>PMID:12586695</ref> <ref>PMID:19521502</ref> <ref>PMID:21454883</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The SEA complex (SEAC) is a growth regulator that acts as a GTPase-activating protein (GAP) towards Gtr1, a Rag GTPase that relays nutrient status to the Target of Rapamycin Complex 1 (TORC1) in yeast(1). Functionally, the SEAC has been divided into two subcomplexes: SEACIT, which has GAP activity and inhibits TORC1, and SEACAT, which regulates SEACIT(2). This system is conserved in mammals: the GATOR complex, consisting of GATOR1 (SEACIT) and GATOR2 (SEACAT), transmits amino acid(3) and glucose(4) signals to mTORC1. Despite its importance, the structure of SEAC/GATOR, and thus molecular understanding of its function, is lacking. Here, we solve the cryo-EM structure of the native eight-subunit SEAC. The SEAC has a modular structure in which a COPII-like cage corresponding to SEACAT binds two flexible wings, which correspond to SEACIT. The wings are tethered to the core via Sea3, which forms part of both modules. The GAP mechanism of GATOR1 is conserved in SEACIT, and GAP activity is unaffected by SEACAT in vitro. In vivo, the wings are essential for recruitment of the SEAC to the vacuole, primarily via the EGO complex. Our results indicate that rather than being a direct inhibitor of SEACIT, SEACAT acts as a scaffold for the binding of TORC1 regulators.
-Authors:
+Cryo-EM structure of the SEA complex.,Tafur L, Hinterndorfer K, Gabus C, Lamanna C, Bergmann A, Sadian Y, Hamdi F, Kyrilis FL, Kastritis PL, Loewith R Nature. 2022 Nov;611(7935):399-404. doi: 10.1038/s41586-022-05370-0. Epub 2022 , Oct 26. PMID:36289347<ref>PMID:36289347</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 8ae6" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Saccharomyces cerevisiae]]
+[[Category: Loewith R]]
+[[Category: Tafur L]]

8ae6

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Current revision

Cryo-EM structure of the SEA complex wing (SEACIT)

Structural highlights

Function

Publication Abstract from PubMed

References

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