Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination.
作者： E. C. Dueber , A. J. Schoeffler , A. Lingel , J. M. Elliott , A. V. Fedorova
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摘要: Inhibitor of apoptosis (IAP) proteins are negative regulators cell death. IAP family members contain RING domains that impart E3 ubiquitin ligase activity. Binding endogenous or small-molecule antagonists to select baculovirus repeat (BIR) within cellular (cIAP) promotes autoubiquitination and proteasomal degradation so releases inhibition mediated by cIAP. Although the molecular details antagonist–BIR domain interactions well understood, it is not clear how this binding event influences activity domain. Here biochemical structural studies reveal unliganded, multidomain cIAP1 sequesters a compact, monomeric structure prevents dimerization. Antagonist induces conformational rearrangements enable dimerization formation active ligase.
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