8auk

Cryo-EM structure of human BIRC6 in complex with HTRA2.

spinqualitylabelsall models 8auk, resolution 6.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8auk is a 5 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 6.2Å Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BIRC6_HUMAN Anti-apoptotic protein which can regulate cell death by controlling caspases and by acting as an E3 ubiquitin-protein ligase. Has an unusual ubiquitin conjugation system in that it could combine in a single polypeptide, ubiquitin conjugating (E2) with ubiquitin ligase (E3) activity, forming a chimeric E2/E3 ubiquitin ligase. Its tragets include CASP9 and DIABLO/SMAC. Acts as an inhibitor of CASP3, CASP7 and CASP9. Important regulator for the final stages of cytokinesis. Crucial for normal vesicle targeting to the site of abscission, but also for the integrity of the midbody and the midbody ring, and its striking ubiquitin modification. Publication Abstract from PubMed Inhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic proteases, keeping them inactive and preventing cell death. The atypical ubiquitin ligase BIRC6 is the only essential IAP, additionally functioning as a suppressor of autophagy. We performed a structure-function analysis of BIRC6 in complex with caspase-9, HTRA2, SMAC, and LC3B, which are critical apoptosis and autophagy proteins. Cryo-electron microscopy structures showed that BIRC6 forms a megadalton crescent shape that arcs around a spacious cavity containing receptor sites for client proteins. Multivalent binding of SMAC obstructs client binding, impeding ubiquitination of both autophagy and apoptotic substrates. On the basis of these data, we discuss how the BIRC6/SMAC complex can act as a stress-induced hub to regulate apoptosis and autophagy drivers. Structural basis for regulation of apoptosis and autophagy by the BIRC6/SMAC complex.,Ehrmann JF, Grabarczyk DB, Heinke M, Deszcz L, Kurzbauer R, Hudecz O, Shulkina A, Gogova R, Meinhart A, Versteeg GA, Clausen T Science. 2023 Mar 17;379(6637):1117-1123. doi: 10.1126/science.ade8873. Epub 2023 , Feb 9. PMID:36758105 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Ubiquitin protein ligase 3D structures

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