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==Cryo-EM structure of the Sec complex from S. cerevisiae, Sec61 pore ring and Sec63 FN3 double mutant, class without Sec62==
<StructureSection load='7kat' size='340' side='right'caption='[[7kat]], [[Resolution|resolution]] 4.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7kat]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_BY4741 Saccharomyces cerevisiae BY4741]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7KAT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7KAT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.4&#8491;</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=7kat FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7kat OCA], [https://pdbe.org/7kat PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7kat RCSB], [https://www.ebi.ac.uk/pdbsum/7kat PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7kat ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SC61A_YEAST SC61A_YEAST] Part of the Sec61 complex, which is the major component of a channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). The functional states of the translocon complex include co- and post-translational ER import, cotranslational membrane protein integration and retrograde transport of misfolded proteins out of the ER. In the cotranslational pathway, ribosomes synthesizing presecretory proteins are targeted to the translocon by the cytosolic signal recognition particle (SRP) and its ER-localized receptor. The association of the Sec61 complex with the ribosome is mediated by the 28S rRNA of the large ribosomal subunit. SRP-independent post-translational translocation requires the association of additional factors, such as the Sec62/63 complex and KAR2. In an initial step, the signal sequence seems to bind simultaneously to SEC61 and SEC62. A cycle of assembly and disassembly of Sec62/63 complex from SEC61 may govern the activity of the translocon. SEC61 mediates the association with the ribosome.
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== Publication Abstract from PubMed ==
Many proteins are transported into the endoplasmic reticulum by the universally conserved Sec61 channel. Post-translational transport requires two additional proteins, Sec62 and Sec63, but their functions are poorly defined. In the present study, we determined cryo-electron microscopy (cryo-EM) structures of several variants of Sec61-Sec62-Sec63 complexes from Saccharomyces cerevisiae and Thermomyces lanuginosus and show that Sec62 and Sec63 induce opening of the Sec61 channel. Without Sec62, the translocation pore of Sec61 remains closed by the plug domain, rendering the channel inactive. We further show that the lateral gate of Sec61 must first be partially opened by interactions between Sec61 and Sec63 in cytosolic and luminal domains, a simultaneous disruption of which completely closes the channel. The structures and molecular dynamics simulations suggest that Sec62 may also prevent lipids from invading the channel through the open lateral gate. Our study shows how Sec63 and Sec62 work together in a hierarchical manner to activate Sec61 for post-translational protein translocation.

Stepwise gating of the Sec61 protein-conducting channel by Sec63 and Sec62.,Itskanov S, Kuo KM, Gumbart JC, Park E Nat Struct Mol Biol. 2021 Feb;28(2):162-172. doi: 10.1038/s41594-020-00541-x. , Epub 2021 Jan 4. PMID:33398175<ref>PMID:33398175</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 7kat" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae BY4741]]
[[Category: Itskanov S]]
[[Category: Park E]]