Vucic D, Kaiser W J, Miller L K
Department of Entomology and the Department of Genetics, The University of Georgia, Athens, Georgia 30602, USA.
J Biol Chem. 1998 Dec 18;273(51):33915-21. doi: 10.1074/jbc.273.51.33915.
A family of antiapoptotic regulators known as inhibitors of apoptosis (IAPs) was initially identified and functionally described in baculoviruses, and IAP homologues are now known in insects, birds, and mammals. Baculovirus and Drosophila IAPs inhibit apoptosis induced by Drosophila proapoptotic proteins Reaper, HID, and GRIM and physically interact with them through their baculovirus IAP repeat (BIR) region. Here we examined the functional importance of BIR and RING finger motifs of Orgyia pseudotsugata nuclear polyhedrosis virus Op-IAP and D-IAP1 in binding to and inhibiting HID. In the absence of both the BIR1 and RING motifs, the BIR2 regions of Op-IAP and D-IAP1 were able to associate with HID and block HID-induced apoptosis. Mutation of conserved amino acid residues within the BIR and RING finger motifs revealed that the conserved residues within BIR2 were essential for Op-IAP to inhibit apoptosis. However, most of the conserved residues of the BIR2 were not required for HID binding. A region at the carboxy-proximal end of BIR2 was essential for the association of Op-IAP with HID. Thus binding to HID is necessary but not sufficient to block HID-induced apoptosis: the conserved residues within BIR2 must have an additional role in blocking apoptosis. These findings demonstrate that the region encompassing a single BIR of Op-IAP and D-IAP1 can be sufficient for physical interaction with and inhibition of apoptosis induced by HID.
一类被称为凋亡抑制因子（IAPs）的抗凋亡调节因子最初是在杆状病毒中被鉴定并进行功能描述的，如今在昆虫、鸟类和哺乳动物中也发现了IAP同源物。杆状病毒和果蝇的IAPs可抑制果蝇促凋亡蛋白收割者（Reaper）、HID和GRIM诱导的凋亡，并通过其杆状病毒IAP重复序列（BIR）区域与它们发生物理相互作用。在此，我们研究了云杉毒蛾核型多角体病毒Op-IAP和D-IAP1的BIR和指环结构域在结合并抑制HID方面的功能重要性。在缺失BIR1和指环基序的情况下，Op-IAP和D-IAP1的BIR2区域能够与HID结合并阻断HID诱导的凋亡。BIR和指环基序内保守氨基酸残基的突变表明，BIR2内的保守残基对于Op-IAP抑制凋亡至关重要。然而，BIR2的大多数保守残基并非HID结合所必需。BIR2羧基近端的一个区域对于Op-IAP与HID的结合至关重要。因此，与HID结合对于阻断HID诱导的凋亡是必要的，但并不充分：BIR2内的保守残基在阻断凋亡方面必定还有其他作用。这些发现表明，包含Op-IAP和D-IAP1单个BIR的区域足以与HID发生物理相互作用并抑制其诱导的凋亡。
