The BIR domain of IAP-like protein 2 is conformationally unstable: implications for caspase inhibition

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dc.contributor.author Shin, Hwain
dc.contributor.author Renatus, Martin
dc.contributor.author Eckelman, Brendan P.
dc.contributor.author Nunes, Viviane Abreu [UNIFESP]
dc.contributor.author Sampaio, Claudio Augusto Machado [UNIFESP]
dc.contributor.author Salvesen, Guy S.
dc.date.accessioned 2016-01-24T12:37:32Z
dc.date.available 2016-01-24T12:37:32Z
dc.date.issued 2005-01-01
dc.identifier http://dx.doi.org/10.1042/BJ20041107
dc.identifier.citation Biochemical Journal. London: Portland Press, v. 385, p. 1-10, 2005.
dc.identifier.issn 0264-6021
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/28055
dc.description.abstract Several IAP (inhibitor of apoptosis) proteins regulate cell fate decisions, and the X-linked IAP (XIAP) does so in part by inhibiting caspases, proteases that execute the apoptotic pathway. A tissue-specific homologue of XIAP, known as ILP2 (IAP-like protein 2), has previously been implicated in the control of apoptosis in the testis by direct inhibition of caspase 9. in examining this protein we found that the putative caspase 9 interaction domain is a surprisingly weak inhibitor and is also conformationally unstable. Comparison with the equivalent domain in XIAP demonstrated that the instability is due to the lack of a linker segment N-terminal to the inhibitory BIR (baculovirus IAP repeat) domain. Fusion of a 9-residue linker from XIAP to the N-terminus of ILP2 restored tight caspase 9 inhibition, dramatically increased conformational stability and allowed crystallization of the ILP2 BIR domain in a form strikingly similar to the XIAP third BIR domain. We conclude that ILP2 is an unstable protein, and cannot inhibit caspase 9 in a physiological way on its own. We speculate that ILP2 requires assistance from unidentified cellular factors to be an effective inhibitor of apoptosis in vivo. en
dc.format.extent 1-10
dc.language.iso eng
dc.publisher Portland Press
dc.relation.ispartof Biochemical Journal
dc.rights Acesso aberto
dc.subject apoptosis en
dc.subject baculovirus IAP repeat (BIR) domain en
dc.subject caspase en
dc.subject crystallography en
dc.subject inhibitor of apoptosis protein (IAP) en
dc.subject spermatogenesis en
dc.title The BIR domain of IAP-like protein 2 is conformationally unstable: implications for caspase inhibition en
dc.type Artigo
dc.contributor.institution Burnham Inst
dc.contributor.institution Univ Calif San Diego
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.description.affiliation Burnham Inst, Program Apoptosis & Cell Death Res, La Jolla, CA 92037 USA
dc.description.affiliation Univ Calif San Diego, Grad Program Mol Pathol, La Jolla, CA 92037 USA
dc.description.affiliation UNIFESP, Escola Paulista Med, Dept Biochem, São Paulo, Brazil
dc.description.affiliationUnifesp UNIFESP, Escola Paulista Med, Dept Biochem, São Paulo, Brazil
dc.identifier.doi 10.1042/BJ20041107
dc.description.source Web of Science
dc.identifier.wos WOS:000226346500001



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