6so5: Difference between revisions
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<StructureSection load='6so5' size='340' side='right'caption='[[6so5]], [[Resolution|resolution]] 4.20Å' scene=''> | <StructureSection load='6so5' size='340' side='right'caption='[[6so5]], [[Resolution|resolution]] 4.20Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6so5]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[6so5]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SO5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SO5 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.2Å</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=' | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6so5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6so5 OCA], [https://pdbe.org/6so5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6so5 RCSB], [https://www.ebi.ac.uk/pdbsum/6so5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6so5 ProSAT]</span></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=6so5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6so5 OCA], [https://pdbe.org/6so5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6so5 RCSB], [https://www.ebi.ac.uk/pdbsum/6so5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6so5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | |||
[https://www.uniprot.org/uniprot/GET3_HUMAN GET3_HUMAN] The disease is caused by variants affecting the gene represented in this entry. | |||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/GET3_HUMAN GET3_HUMAN] 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/WRB and CAMLG/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-CAMLG receptor, and returning it to the cytosol to initiate a new round of targeting. May be involved in insulin signaling.[HAMAP-Rule:MF_03112]<ref>PMID:17382883</ref> <ref>PMID:18477612</ref> <ref>PMID:23041287</ref> <ref>PMID:25535373</ref> <ref>PMID:31461301</ref> | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Flemming | [[Category: Flemming D]] | ||
[[Category: Heimes | [[Category: Heimes M]] | ||
[[Category: McDowell | [[Category: McDowell MA]] | ||
[[Category: Sinning | [[Category: Sinning I]] | ||
[[Category: Wild | [[Category: Wild K]] | ||
Latest revision as of 11:52, 14 July 2024
Homo sapiens WRB/CAML heterotetramer in complex with a TRC40 dimerHomo sapiens WRB/CAML heterotetramer in complex with a TRC40 dimer
Structural highlights
DiseaseGET3_HUMAN The disease is caused by variants affecting the gene represented in this entry. FunctionGET3_HUMAN 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/WRB and CAMLG/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-CAMLG receptor, and returning it to the cytosol to initiate a new round of targeting. May be involved in insulin signaling.[HAMAP-Rule:MF_03112][1] [2] [3] [4] [5] Publication Abstract from PubMedMembrane protein biogenesis faces the challenge of chaperoning hydrophobic transmembrane helices for faithful membrane insertion. The guided entry of tail-anchored proteins (GET) pathway targets and inserts tail-anchored (TA) proteins into the endoplasmic reticulum (ER) membrane with an insertase (yeast Get1/Get2 or mammalian WRB/CAML) that captures the TA from a cytoplasmic chaperone (Get3 or TRC40, respectively). Here, we present cryo-electron microscopy reconstructions, native mass spectrometry, and structure-based mutagenesis of human WRB/CAML/TRC40 and yeast Get1/Get2/Get3 complexes. Get3 binding to the membrane insertase supports heterotetramer formation, and phosphatidylinositol binding at the heterotetramer interface stabilizes the insertase for efficient TA insertion in vivo. We identify a Get2/CAML cytoplasmic helix that forms a "gating" interaction with Get3/TRC40 important for TA insertion. Structural homology with YidC and the ER membrane protein complex (EMC) implicates an evolutionarily conserved insertion mechanism for divergent substrates utilizing a hydrophilic groove. Thus, we provide a detailed structural and mechanistic framework to understand TA membrane insertion. Structural Basis of Tail-Anchored Membrane Protein Biogenesis by the GET Insertase Complex.,McDowell MA, Heimes M, Fiorentino F, Mehmood S, Farkas A, Coy-Vergara J, Wu D, Bolla JR, Schmid V, Heinze R, Wild K, Flemming D, Pfeffer S, Schwappach B, Robinson CV, Sinning I Mol Cell. 2020 Oct 1;80(1):72-86.e7. doi: 10.1016/j.molcel.2020.08.012. Epub 2020, Sep 9. PMID:32910895[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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