Amsacta moorei Entomopoxvirus inhibitor of apoptosis suppresses cell death by binding Grim and Hid.

Amsacta moorei Entomopoxvirus inhibitor of apoptosis suppresses cell death by binding Grim and Hid.
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Amsacta moorei 昆虫痘病毒凋亡抑制剂通过结合 Grim 和 Hid 来抑制细胞死亡。

DOI:
10.1128/jvi.79.6.3684-3691.2005
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发表时间:
2005
影响因子:
5.4
通讯作者:
Moyer,RichardW
Moyer,RichardW
中科院分区:
医学2区
文献类型:
--
作者:
Li,Qianjun;Liston,Peter;Schokman,Natasha;Ho,JennyMei;Moyer,RichardW

文献摘要

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细胞凋亡抑制因子(Inhibitor of apoptosis,iap)基因已在杆状病毒科和昆虫痘病毒亚科两个独立的昆虫病毒科的基因组中发现。在这份报告中,我们研究了木蠹蛾单痘病毒编码的IAP蛋白(AMV-IAP)的功能属性。利用噬菌体随机肽库研究了AMV-IAP的杆状病毒IAP重复序列(BIR)的结合特异性,并鉴定了与Reaper/Hid/Grim家族果蝇亲嗜性蛋白氨基末端相似的序列。此外,AMV-IAP蛋白的BIR结构域被证明通过AVPI四肽序列结合哺乳动物IAP抑制剂Smac,这表明在昆虫和哺乳动物IAP中发现的肽结合口袋和凹槽在该病毒蛋白中是保守的。相互作用分析表明BIR 1是Grim的高亲和力位点,而BIR 2与Hid的相互作用更强。Grim和Hid都被证明在体内与AMV-IAP相互作用,当AMV-IAP共表达时,Grim或Hid诱导的细胞死亡被抑制。
Inhibitor of apoptosis (iap) genes have been identified in the genomes of two independent families of insect viruses, theBaculoviridaeand theEntomopoxvirinae. In this report, we examined the functional attributes of theAmsacta mooreientomopoxvirus-encoded IAP protein (AMV-IAP). The binding specificity of the individual baculoviral IAP repeat (BIR) domains of AMV-IAP was investigated by using a random-peptide, phage display library, and sequences similar to the amino termini of proapoptoticDrosophilaproteins in the Reaper/Hid/Grim family were identified. Furthermore, the BIR domains of AMV-IAP protein were demonstrated to bind the mammalian IAP inhibitor Smac through the AVPI tetrapeptide sequence, suggesting that the peptide binding pocket and groove found in the insect and mammalian IAPs is conserved in this viral protein. Interaction analysis implicated BIR1 as the high-affinity site for Grim, while BIR2 interacted more strongly with Hid. Both Grim and Hid were demonstrated to interact with AMV-IAP in vivo, and Grim- or Hid-induced cell death was suppressed when AMV-IAP was coexpressed.