Please use this identifier to cite or link to this item: https://repositorio.unifesp.br/handle/11600/28055
Title: The BIR domain of IAP-like protein 2 is conformationally unstable: implications for caspase inhibition
Authors: Shin, Hwain
Renatus, Martin
Eckelman, Brendan P.
Nunes, Viviane Abreu [UNIFESP]
Sampaio, Claudio Augusto Machado [UNIFESP]
Salvesen, Guy S.
Burnham Inst
Univ Calif San Diego
Universidade Federal de São Paulo (UNIFESP)
Keywords: apoptosis
baculovirus IAP repeat (BIR) domain
caspase
crystallography
inhibitor of apoptosis protein (IAP)
spermatogenesis
Issue Date: 1-Jan-2005
Publisher: Portland Press
Citation: Biochemical Journal. London: Portland Press, v. 385, p. 1-10, 2005.
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.
URI: http://repositorio.unifesp.br/handle/11600/28055
ISSN: 0264-6021
Other Identifiers: http://dx.doi.org/10.1042/BJ20041107
Appears in Collections:Artigo

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.