View source for 5bw8


==2.8 A crystal structure of a Get3-Get4-Get5 intermediate complex from S.cerevisiae==
<StructureSection load='5bw8' size='340' side='right'caption='[[5bw8]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5bw8]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae], [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=5BW8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5BW8 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]] 2.8&#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=5bw8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5bw8 OCA], [https://pdbe.org/5bw8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5bw8 RCSB], [https://www.ebi.ac.uk/pdbsum/5bw8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5bw8 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> 
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== 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<ref>PMID:26451041</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5bw8" style="background-color:#fffaf0;"></div>

==See Also==
*[[ATPase 3D structures|ATPase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae RM11-1a]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Chartron JW]]
[[Category: Clemons WM]]
[[Category: Gristick HB]]