6z3t

Structure of canine Sec61 inhibited by mycolactone

spinqualitylabelsall models 6z3t, resolution 2.69Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6z3t is a 3 chain structure with sequence from Canis lupus familiaris. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.69Å Ligands: Q6B Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function S61A1_CANLF Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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