View source for 4pwx


==Crystal structure of an ATP-bound Get3-Get4-Get5 complex from S.cerevisiae==
<StructureSection load='4pwx' size='340' side='right'caption='[[4pwx]], [[Resolution|resolution]] 5.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4pwx]] is a 6 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=4PWX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PWX 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]] 5.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <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=4pwx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pwx OCA], [https://pdbe.org/4pwx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4pwx RCSB], [https://www.ebi.ac.uk/pdbsum/4pwx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4pwx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GET3_YEAST 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.<ref>PMID:12680698</ref> <ref>PMID:16269340</ref> <ref>PMID:18724936</ref> <ref>PMID:21866104</ref> <ref>PMID:21719644</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Correct localization of membrane proteins is essential to all cells. Chaperone cascades coordinate the capture and handover of substrate proteins from the ribosomes to the target membranes, yet the mechanistic and structural details of these processes remain unclear. Here we investigate the conserved GET pathway, in which the Get4-Get5 complex mediates the handover of tail-anchor (TA) substrates from the cochaperone Sgt2 to the Get3 ATPase, the central targeting factor. We present a crystal structure of a yeast Get3-Get4-Get5 complex in an ATP-bound state and show how Get4 primes Get3 by promoting the optimal configuration for substrate capture. Structure-guided biochemical analyses demonstrate that Get4-mediated regulation of ATP hydrolysis by Get3 is essential to efficient TA-protein targeting. Analogous regulation of other chaperones or targeting factors could provide a general mechanism for ensuring effective substrate capture during protein biogenesis.

Crystal structure of ATP-bound Get3-Get4-Get5 complex reveals regulation of Get3 by Get4.,Gristick HB, Rao M, Chartron JW, Rome ME, Shan SO, Clemons WM Jr Nat Struct Mol Biol. 2014 May;21(5):437-42. doi: 10.1038/nsmb.2813. Epub 2014 Apr, 13. PMID:24727835<ref>PMID:24727835</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4pwx" style="background-color:#fffaf0;"></div>

==See Also==
*[[ATPase 3D structures|ATPase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Clemons Jr WM]]
[[Category: Gristick HB]]