6x90

From Proteopedia

(Difference between revisions)

Current revision

Structure of the guanine nucleotide exchange factor Sec12 bound to the small GTPase Sar1

Structural highlights

6x90 is a 2 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.26Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SEC12_YEAST Guanine nucleotide-exchange factor (GEF) required for the formation or budding of transport vesicles from the ER. This function involves the cytoplasmic domain of the protein, which is thought to interact with the small GTP-binding protein SAR1. Required for autophagy.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14] ^[15] ^[16]

Publication Abstract from PubMed

The first stage of the eukaryotic secretory pathway is the packaging of cargo proteins into coat protein complex II (COPII) vesicles exiting the ER. The cytoplasmic COPII vesicle coat machinery is recruited to the ER membrane by the activated, GTP-bound, form of the conserved Sar1 GTPase. Activation of Sar1 on the surface of the ER by Sec12, a membrane-anchored GEF (guanine nucleotide exchange factor), is therefore the initiating step of the secretory pathway. Here we report the structure of the complex between Sar1 and the cytoplasmic GEF domain of Sec12, both from Saccharomyces cerevisiae. This structure, representing a key nucleotide-free activation intermediate, reveals how the potassium ion-binding K loop disrupts the nucleotide-binding site of Sar1. We propose an unexpected orientation of the GEF domain relative to the membrane surface and postulate a mechanism for how Sec12 facilitates membrane insertion of the amphipathic helix exposed by Sar1 upon GTP binding.

Structural basis for the initiation of COPII vesicle biogenesis.,Joiner AMN, Fromme JC Structure. 2021 Aug 5;29(8):859-872.e6. doi: 10.1016/j.str.2021.03.013. Epub 2021 , Apr 7. PMID:33831355^[17]

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

References

↑ Ishihara N, Hamasaki M, Yokota S, Suzuki K, Kamada Y, Kihara A, Yoshimori T, Noda T, Ohsumi Y. Autophagosome requires specific early Sec proteins for its formation and NSF/SNARE for vacuolar fusion. Mol Biol Cell. 2001 Nov;12(11):3690-702. PMID:11694599
↑ Hamasaki M, Noda T, Ohsumi Y. The early secretory pathway contributes to autophagy in yeast. Cell Struct Funct. 2003 Feb;28(1):49-54. PMID:12655150
↑ Hardwick KG, Boothroyd JC, Rudner AD, Pelham HR. Genes that allow yeast cells to grow in the absence of the HDEL receptor. EMBO J. 1992 Nov;11(11):4187-95. PMID:1327759
↑ Futai E, Schekman R. Purification and functional properties of yeast Sec12 GEF. Methods Enzymol. 2005;404:74-82. PMID:16413259 doi:http://dx.doi.org/10.1016/S0076-6879(05)04008-5
↑ Rexach MF, Schekman RW. Distinct biochemical requirements for the budding, targeting, and fusion of ER-derived transport vesicles. J Cell Biol. 1991 Jul;114(2):219-29. PMID:1649197
↑ d'Enfert C, Wuestehube LJ, Lila T, Schekman R. Sec12p-dependent membrane binding of the small GTP-binding protein Sar1p promotes formation of transport vesicles from the ER. J Cell Biol. 1991 Aug;114(4):663-70. PMID:1907973
↑ Oka T, Nishikawa S, Nakano A. Reconstitution of GTP-binding Sar1 protein function in ER to Golgi transport. J Cell Biol. 1991 Aug;114(4):671-9. PMID:1907974
↑ d'Enfert C, Barlowe C, Nishikawa S, Nakano A, Schekman R. Structural and functional dissection of a membrane glycoprotein required for vesicle budding from the endoplasmic reticulum. Mol Cell Biol. 1991 Nov;11(11):5727-34. PMID:1922074
↑ Nakano A, Muramatsu M. A novel GTP-binding protein, Sar1p, is involved in transport from the endoplasmic reticulum to the Golgi apparatus. J Cell Biol. 1989 Dec;109(6 Pt 1):2677-91. PMID:2512296
↑ Nakano A, Brada D, Schekman R. A membrane glycoprotein, Sec12p, required for protein transport from the endoplasmic reticulum to the Golgi apparatus in yeast. J Cell Biol. 1988 Sep;107(3):851-63. PMID:3047151
↑ Novick P, Field C, Schekman R. Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway. Cell. 1980 Aug;21(1):205-15. PMID:6996832
↑ Nishikawa S, Hirata A, Nakano A. Inhibition of endoplasmic reticulum (ER)-to-Golgi transport induces relocalization of binding protein (BiP) within the ER to form the BiP bodies. Mol Biol Cell. 1994 Oct;5(10):1129-43. PMID:7865879
↑ Oka T, Nakano A. Inhibition of GTP hydrolysis by Sar1p causes accumulation of vesicles that are a functional intermediate of the ER-to-Golgi transport in yeast. J Cell Biol. 1994 Feb;124(4):425-34. PMID:8106544
↑ Barlowe C, Schekman R. SEC12 encodes a guanine-nucleotide-exchange factor essential for transport vesicle budding from the ER. Nature. 1993 Sep 23;365(6444):347-9. PMID:8377826 doi:http://dx.doi.org/10.1038/365347a0
↑ Barlowe C, Schekman R. Expression, purification, and assay of Sec12p: a Sar1p-specific GDP dissociation stimulator. Methods Enzymol. 1995;257:98-106. PMID:8583945
↑ Campbell JL, Schekman R. Selective packaging of cargo molecules into endoplasmic reticulum-derived COPII vesicles. Proc Natl Acad Sci U S A. 1997 Feb 4;94(3):837-42. PMID:9023343
↑ Joiner AMN, Fromme JC. Structural basis for the initiation of COPII vesicle biogenesis. Structure. 2021 Aug 5;29(8):859-872.e6. PMID:33831355 doi:10.1016/j.str.2021.03.013

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6x90"

Categories: Large Structures | Saccharomyces cerevisiae S288C | Fromme JC | Joiner AMN

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 6x90 is ON HOLD  until Paper Publication
+==Structure of the guanine nucleotide exchange factor Sec12 bound to the small GTPase Sar1==
+<StructureSection load='6x90' size='340' side='right'caption='[[6x90]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6x90]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6X90 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6X90 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.26&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</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=6x90 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x90 OCA], [https://pdbe.org/6x90 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x90 RCSB], [https://www.ebi.ac.uk/pdbsum/6x90 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x90 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/SEC12_YEAST SEC12_YEAST] Guanine nucleotide-exchange factor (GEF) required for the formation or budding of transport vesicles from the ER. This function involves the cytoplasmic domain of the protein, which is thought to interact with the small GTP-binding protein SAR1. Required for autophagy.<ref>PMID:11694599</ref> <ref>PMID:12655150</ref> <ref>PMID:1327759</ref> <ref>PMID:16413259</ref> <ref>PMID:1649197</ref> <ref>PMID:1907973</ref> <ref>PMID:1907974</ref> <ref>PMID:1922074</ref> <ref>PMID:2512296</ref> <ref>PMID:3047151</ref> <ref>PMID:6996832</ref> <ref>PMID:7865879</ref> <ref>PMID:8106544</ref> <ref>PMID:8377826</ref> <ref>PMID:8583945</ref> <ref>PMID:9023343</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The first stage of the eukaryotic secretory pathway is the packaging of cargo proteins into coat protein complex II (COPII) vesicles exiting the ER. The cytoplasmic COPII vesicle coat machinery is recruited to the ER membrane by the activated, GTP-bound, form of the conserved Sar1 GTPase. Activation of Sar1 on the surface of the ER by Sec12, a membrane-anchored GEF (guanine nucleotide exchange factor), is therefore the initiating step of the secretory pathway. Here we report the structure of the complex between Sar1 and the cytoplasmic GEF domain of Sec12, both from Saccharomyces cerevisiae. This structure, representing a key nucleotide-free activation intermediate, reveals how the potassium ion-binding K loop disrupts the nucleotide-binding site of Sar1. We propose an unexpected orientation of the GEF domain relative to the membrane surface and postulate a mechanism for how Sec12 facilitates membrane insertion of the amphipathic helix exposed by Sar1 upon GTP binding.
-Authors:
+Structural basis for the initiation of COPII vesicle biogenesis.,Joiner AMN, Fromme JC Structure. 2021 Aug 5;29(8):859-872.e6. doi: 10.1016/j.str.2021.03.013. Epub 2021 , Apr 7. PMID:33831355<ref>PMID:33831355</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 6x90" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Saccharomyces cerevisiae S288C]]
+[[Category: Fromme JC]]
+[[Category: Joiner AMN]]

6x90

From Proteopedia

Current revision

Structure of the guanine nucleotide exchange factor Sec12 bound to the small GTPase Sar1

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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