X-ray crystal structure and functional analysis of vaccinia virus K3L reveals molecular determinants for PKR subversion and substrate recognition

被引：79
作者：
Dar, AC
Sicheri, F
机构：
[1] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Mol Biol & Canc, Toronto, ON M5G 1X5, Canada
[2] Univ Toronto, Dept Mol & Med Genet, Toronto, ON M5S 1A8, Canada
来源：
MOLECULAR CELL | 2002年 / 10卷 / 02期
关键词：
D O I：
10.1016/S1097-2765(02)00590-7
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The vaccinia virus protein K3L subverts the mammalian antiviral defense mechanism by inhibiting the RNA-dependent protein kinase PKR. K3L is a structural mimic of PKR's natural substrate, the translation initiation factor eIF2alpha. To further our understanding of K3L inhibitory function and PKR substrate recognition, we have solved the 1.8 Angstrom X-ray crystal structure of K3L. The structure consists of a five-strand beta barrel with an intervening helix insert region similar in topology to the functionally divergent S1 domain. Mutational analysis identifies two proximal regions of the K3L structure as possessing specialized PKR binding and inhibitory function. Further analysis reveals that PKR dimerization composes a key switch that regulates both its catalytic activation and its molecular recognition of K3L and eIF2alpha.
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页码：295 / 305
页数：11
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