6z3t

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Current revision (10:23, 22 May 2024) (edit) (undo)
 
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==Structure of canine Sec61 inhibited by mycolactone==
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<StructureSection load='6z3t' size='340' side='right'caption='[[6z3t]]' scene=''>
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<StructureSection load='6z3t' size='340' side='right'caption='[[6z3t]], [[Resolution|resolution]] 2.69&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6z3t]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Canis_lupus_familiaris Canis lupus familiaris]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Z3T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z3T FirstGlance]. <br>
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</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6z3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z3t OCA], [http://pdbe.org/6z3t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6z3t RCSB], [http://www.ebi.ac.uk/pdbsum/6z3t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6z3t ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.69&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=Q6B:[(6~{S},7~{S},9~{Z},12~{R})-12-[(~{Z},2~{S},6~{R},7~{R},9~{R})-4,6-dimethyl-7,9-bis(oxidanyl)dec-4-en-2-yl]-7,9-dimethyl-2-oxidanylidene-1-oxacyclododec-9-en-6-yl]+(2~{E},4~{E},6~{E},8~{E},10~{E},12~{S},13~{S},15~{S})-4,6,10-trimethyl-12,13,15-tris(oxidanyl)hexadeca-2,4,6,8,10-pentaenoate'>Q6B</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6z3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z3t OCA], [https://pdbe.org/6z3t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z3t RCSB], [https://www.ebi.ac.uk/pdbsum/6z3t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z3t ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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[https://www.uniprot.org/uniprot/S61A1_CANLF S61A1_CANLF]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Protein secretion in eukaryotes and prokaryotes involves a universally conserved protein translocation channel formed by the Sec61 complex. Unrelated small-molecule natural products and synthetic compounds inhibit Sec61 with differential effects for different substrates or for Sec61 from different organisms, making this a promising target for therapeutic intervention. To understand the mode of inhibition and provide insight into the molecular mechanism of this dynamic translocon, we determined the structure of mammalian Sec61 inhibited by the Mycobacterium ulcerans exotoxin mycolactone via electron cryo-microscopy. Unexpectedly, the conformation of inhibited Sec61 is optimal for substrate engagement, with mycolactone wedging open the cytosolic side of the lateral gate. The inability of mycolactone-inhibited Sec61 to effectively transport substrate proteins implies that signal peptides and transmembrane domains pass through the site occupied by mycolactone. This provides a foundation for understanding the molecular mechanism of Sec61 inhibitors and reveals novel features of translocon function and dynamics.
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Structure of the Inhibited State of the Sec Translocon.,Gerard SF, Hall BS, Zaki AM, Corfield KA, Mayerhofer PU, Costa C, Whelligan DK, Biggin PC, Simmonds RE, Higgins MK Mol Cell. 2020 Aug 6;79(3):406-415.e7. doi: 10.1016/j.molcel.2020.06.013. Epub, 2020 Jul 9. PMID:32692975<ref>PMID:32692975</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6z3t" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Canis lupus familiaris]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Z-disk]]
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[[Category: Gerard SF]]
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[[Category: Higgins MK]]

Current revision

Structure of canine Sec61 inhibited by mycolactone

PDB ID 6z3t

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