Mechanism of the interaction between the intrinsically disordered C-terminus of the pro-apoptotic ARTS protein and the Bir3 domain of XIAP.

ABSTRACT: ARTS (Sept4_i2) is a mitochondrial pro-apoptotic protein that functions as a tumor suppressor. Its expression is significantly reduced in leukemia and lymphoma patients. ARTS binds and inhibits XIAP (X-linked Inhibitor of Apoptosis protein) by interacting with its Bir3 domain. ARTS promotes degradation of XIAP through the proteasome pathway. By doing so, ARTS removes XIAP inhibition of caspases and enables apoptosis to proceed. ARTS contains 27 unique residues in its C-terminal domain (CTD, residues 248-274) which are important for XIAP binding. Here we characterized the molecular details of this interaction. Biophysical and computational methods were used to show that the ARTS CTD is intrinsically disordered under physiological conditions. Direct binding of ARTS CTD to Bir3 was demonstrat

SUBMITTER: Reingewertz TH 

PROVIDER: S-EPMC3176765 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature