3d9u

Publication Abstract from PubMed

The inhibitor of apoptosis protein (IAP) family of molecules inhibit apoptosis through the suppression of caspase activity. It is known that the XIAP protein regulates both caspase-3 and caspase-9 through direct protein-protein interactions. Specifically, the BIR3 domain of XIAP binds to caspase-9 via a ;hotspot' interaction in which the N-terminal residues of caspase-9 bind in a shallow groove on the surface of XIAP. This interaction is regulated via SMAC, the N-terminus of which binds in the same groove, thus displacing caspase-9. The mechanism of suppression of apoptosis by cIAP1 is less clear. The structure of the BIR3 domain of cIAP1 (cIAP1-BIR3) in complex with N-terminal peptides from both SMAC and caspase-9 has been determined. The binding constants of these peptides to cIAP1-BIR3 have also been determined using the surface plasmon resonance technique. The structures show that the peptides interact with cIAP1 in the same way that they interact with XIAP: both peptides bind in a similar shallow groove in the BIR3 surface, anchored at the N-terminus by a charge-stabilized hydrogen bond. The binding data show that the SMAC and caspase-9 peptides bind with comparable affinities (85 and 48 nM, respectively).

The structure of the BIR3 domain of cIAP1 in complex with the N-terminal peptides of SMAC and caspase-9.,Kulathila R, Vash B, Sage D, Cornell-Kennon S, Wright K, Koehn J, Stams T, Clark K, Price A Acta Crystallogr D Biol Crystallogr. 2009 Jan;65(Pt 1):58-66. Epub 2008, Dec 18. PMID:19153467^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.