3T6P

IAP antagonist-induced conformational change in cIAP1 promotes E3 ligase activation via dimerization

Summary for 3T6P

• Entry DOI: 10.2210/pdb3t6p/pdb
• Descriptor: Baculoviral IAP repeat-containing protein 2, ZINC ION (3 entities in total)
• Functional Keywords: ring, bir, card, uba, apoptosis, e3, ubiquitin ligase, smac/diablo, ubiquitin, caspase, iap family, smac mimetic
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (Potential): Q13490
• Total number of polymer chains: 1
• Total formula weight: 39473.38

Authors

Dueber, E.C.,Schoeffler, A.J.,Lingel, A.,Elliott, M.,Fedorova, A.V.,Giannetti, A.M.,Zobel, K.,Maurer, B.,Varfolomeev, E.,Wu, P.,Wallweber, H.,Hymowitz, S.,Deshayes, K.,Vucic, D.,Fairbrother, W.J. (deposition date: 2011-07-28, release date: 2011-11-02, Last modification date: 2024-02-28)

Primary citation

Dueber, E.C.,Schoeffler, A.J.,Lingel, A.,Elliott, J.M.,Fedorova, A.V.,Giannetti, A.M.,Zobel, K.,Maurer, B.,Varfolomeev, E.,Wu, P.,Wallweber, H.J.,Hymowitz, S.G.,Deshayes, K.,Vucic, D.,Fairbrother, W.J.
Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination.
Science, 334:376-380, 2011

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

PubMed: 22021857
DOI: 10.1126/science.1207862

Experimental method

X-RAY DIFFRACTION (1.897 Å)