title: Oligomerization and activation of caspase-9, induced by Apaf-1 CARD.
abstract: Apaf-1 facilitates the proteolytic activation of procaspase-9 and maintains the hyperactive state of the processed caspase-9. The underlying molecular mechanisms for these activities remain poorly characterized. Here we report that the isolated Apaf-1 caspase recruitment domain (CARD) forms a large hetero-oligomer with the active caspase-9. The catalytic activity of caspase-9 is significantly enhanced in this complex, demonstrating that Apaf-1 CARD allosterically up-regulates caspase-9 activity. Point mutations that inactivate the interactions between Apaf-1 CARD and the prodomain of caspase-9 also abolished the formation of this complex. Based on these observations, we discuss the implications of this complex on the observed Apaf-1 function.
authors.affiliation: Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA.
authors.forename: Eric N
authors.initials: EN
authors.lastname: Shiozaki
authors.forename: Jijie
authors.initials: J
authors.lastname: Chai
authors.forename: Yigong
authors.initials: Y
authors.lastname: Shi
mesh_terms: D053477:Apoptotic Protease-Activating Factor 1; D053453:Caspase 9; D020169:Caspases / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D004789:Enzyme Activation; D008961:Models, Structural; D011506:Proteins / Q000737:chemistry* / Q000502:physiology
chemical_list: D053477:Apoptotic Protease-Activating Factor 1; D011506:Proteins; D053453:Caspase 9; D020169:Caspases