View source for 7spz


==Nucleotide-free Get3 in two open forms==
<StructureSection load='7spz' size='340' side='right'caption='[[7spz]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7spz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Giardia_lamblia_ATCC_50803 Giardia lamblia ATCC 50803]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SPZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SPZ 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]] 3&#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=7spz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7spz OCA], [https://pdbe.org/7spz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7spz RCSB], [https://www.ebi.ac.uk/pdbsum/7spz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7spz ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ASNA_GIAIC ASNA_GIAIC] 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, 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 membrane-bound receptor, and returning it to the cytosol to initiate a new round of targeting.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Tail-anchored (TA) membrane proteins, accounting for roughly 2% of proteomes, are primarily targeted posttranslationally to the endoplasmic reticulum membrane by the guided entry of TA proteins (GET) pathway. For this complicated process, it remains unknown how the central targeting factor Get3 uses nucleotide to facilitate large conformational changes to recognize then bind clients while also preventing exposure of hydrophobic surfaces. Here, we identify the GET pathway in Giardia intestinalis and present the structure of the Get3-client complex in the critical postnucleotide-hydrolysis state, demonstrating that Get3 reorganizes the client-binding domain (CBD) to accommodate and shield the client transmembrane helix. Four additional structures of GiGet3, spanning the nucleotide-free (apo) open to closed transition and the ATP-bound state, reveal the details of nucleotide stabilization and occluded CBD. This work resolves key conundrums and allows for a complete model of the dramatic conformational landscape of Get3.

Structurally derived universal mechanism for the catalytic cycle of the tail-anchored targeting factor Get3.,Fry MY, Najdrova V, Maggiolo AO, Saladi SM, Dolezal P, Clemons WM Jr Nat Struct Mol Biol. 2022 Jul 18. pii: 10.1038/s41594-022-00798-4. doi:, 10.1038/s41594-022-00798-4. PMID:35851188<ref>PMID:35851188</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7spz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Giardia lamblia ATCC 50803]]
[[Category: Large Structures]]
[[Category: Clemons Jr WM]]
[[Category: Fry MY]]
[[Category: Maggiolo AO]]