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5bwk

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6.0 A Crystal structure of a Get3-Get4-Get5 intermediate complex from S.cerevisiae

Structural highlights

5bwk is a 24 chain structure with sequence from Saccharomyces cerevisiae RM11-1a and 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 6Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GET3_YEAST ATPase required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets to the endoplasmic reticulum by membrane-bound receptors GET1 and GET2, where the tail-anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis. ATP binding drives the homodimer towards the closed dimer state, facilitating recognition of newly synthesized TA membrane proteins. ATP hydrolysis is required for insertion. Subsequently, the homodimer reverts towards the open dimer state, lowering its affinity for the GET1-GET2 receptor, and returning it to the cytosol to initiate a new round of targeting. Cooperates with the HDEL receptor ERD2 to mediate the ATP-dependent retrieval of resident ER proteins that contain a C-terminal H-D-E-L retention signal from the Golgi to the ER. Involved in low-level resistance to the oxyanions arsenite and arsenate, and in heat tolerance.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Tail-anchored (TA) proteins, defined as having a single transmembrane helix at their C-terminus, are post-translationally targeted to the endoplasmic reticulum (ER) membrane by the GET (Guided Entry of TA proteins) pathway. In yeast, the handover of TA substrates is mediated by the heterotetrameric Get4/Get5 (Get4/5) complex, which tethers the co-chaperone Sgt2 to the targeting factor, the Get3 ATPase. Binding of Get4/5 to Get3 is critical for efficient TA targeting; however, questions remain about the formation of the Get3-Get4/5 complex. Here we report crystal structures of a Get3-Get4/5 complex from Saccharomyces cerevisiae (Sc) at 2.8 A and 6.0 A, which reveal a novel interface between Get3 and Get4 dominated by electrostatic interactions. Kinetic and mutational analyses strongly suggest that these structures represent an on-pathway intermediate that rapidly assembles and then rearranges to the final Get3-Get4/5 complex. Furthermore, we provide evidence that the Get3-Get4/5 complex is dominated by a single Get4/5 heterotetramer bound to one monomer of a Get3 dimer, uncovering an intriguing asymmetry in the Get4/5 heterotetramer upon Get3 binding. Ultrafast diffusion-limitd electrostatically driven Get3-Get4/5 association enables Get4/5 to rapidly sample and capture Get3 at different stages of the GET pathway.

Mechanism of assembly of a substrate-transfer complex during tail-anchored protein targeting.,Gristick HB, Rome ME, Chartron JW, Rao M, Hess S, Shan SO, Clemons WM Jr J Biol Chem. 2015 Oct 7. pii: jbc.M115.677328. PMID:26451041^[6]

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

References

↑ Shen J, Hsu CM, Kang BK, Rosen BP, Bhattacharjee H. The Saccharomyces cerevisiae Arr4p is involved in metal and heat tolerance. Biometals. 2003 Sep;16(3):369-78. PMID:12680698
↑ Schuldiner M, Collins SR, Thompson NJ, Denic V, Bhamidipati A, Punna T, Ihmels J, Andrews B, Boone C, Greenblatt JF, Weissman JS, Krogan NJ. Exploration of the function and organization of the yeast early secretory pathway through an epistatic miniarray profile. Cell. 2005 Nov 4;123(3):507-19. PMID:16269340 doi:S0092-8674(05)00868-8
↑ Schuldiner M, Metz J, Schmid V, Denic V, Rakwalska M, Schmitt HD, Schwappach B, Weissman JS. The GET complex mediates insertion of tail-anchored proteins into the ER membrane. Cell. 2008 Aug 22;134(4):634-45. PMID:18724936 doi:S0092-8674(08)00777-0
↑ Mariappan M, Mateja A, Dobosz M, Bove E, Hegde RS, Keenan RJ. The mechanism of membrane-associated steps in tail-anchored protein insertion. Nature. 2011 Aug 24;477(7362):61-6. doi: 10.1038/nature10362. PMID:21866104 doi:10.1038/nature10362
↑ Stefer S, Reitz S, Wang F, Wild K, Pang YY, Schwarz D, Bomke J, Hein C, Lohr F, Bernhard F, Denic V, Dotsch V, Sinning I. Structural Basis for Tail-Anchored Membrane Protein Biogenesis by the Get3-Receptor Complex. Science. 2011 Jun 30. PMID:21719644 doi:10.1126/science.1207125
↑ Gristick HB, Rome ME, Chartron JW, Rao M, Hess S, Shan SO, Clemons WM Jr. Mechanism of assembly of a substrate-transfer complex during tail-anchored protein targeting. J Biol Chem. 2015 Oct 7. pii: jbc.M115.677328. PMID:26451041 doi:http://dx.doi.org/10.1074/jbc.M115.677328

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/5bwk"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[5bwk]] is a 24 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_RM11-1a Saccharomyces cerevisiae RM11-1a] and [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=5BWK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BWK FirstGlance]. <br>
-</td></tr><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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 6&#8491;</td></tr>
+<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=5bwk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bwk OCA], [https://pdbe.org/5bwk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bwk RCSB], [https://www.ebi.ac.uk/pdbsum/5bwk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bwk ProSAT]</span></td></tr>
 </table>

5bwk

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Current revision

6.0 A Crystal structure of a Get3-Get4-Get5 intermediate complex from S.cerevisiae

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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