8e2j
From Proteopedia
Cryo-EM structure of BIRC6/Smac (from local refinement 1)
Structural highlights
Publication Abstract from PubMedTight regulation of apoptosis is essential for metazoan development and prevents diseases such as cancer and neurodegeneration. Caspase activation is central to apoptosis, and inhibitor of apoptosis proteins (IAPs) are the principal actors that restrain caspase activity and are therefore attractive therapeutic targets. IAPs, in turn, are regulated by mitochondria-derived proapoptotic factors such as SMAC and HTRA2. Through a series of cryo-electron microscopy structures of full-length human baculoviral IAP repeat-containing protein 6 (BIRC6) bound to SMAC, caspases, and HTRA2, we provide a molecular understanding for BIRC6-mediated caspase inhibition and its release by SMAC. The architecture of BIRC6, together with near-irreversible binding of SMAC, elucidates how the IAP inhibitor SMAC can effectively control a processive ubiquitin ligase to respond to apoptotic stimuli. Structures of BIRC6-client complexes provide a mechanism of SMAC-mediated release of caspases.,Hunkeler M, Jin CY, Fischer ES Science. 2023 Mar 17;379(6637):1105-1111. doi: 10.1126/science.ade5750. Epub 2023 , Feb 9. PMID:36758104[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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