SARS冠状病毒PLpro蛋白酶的结构与功能

Structure and Functions of Papain-like Protease of Severe Acute Respiratory Syndrome(SARS) Coronavirus

SARS冠状病毒基因组编码2种病毒蛋白酶,即木瓜样蛋白酶(PLpro)和3C样蛋白酶(3CLpro).其中,PLpro蛋白酶结构与功能研究是近年来冠状病毒分子生物学研究的热点之一.PLpro蛋白酶参与SARS冠状病毒1a(1ab)复制酶多聚蛋白N端部分的切割加工,是SARS冠状病毒复制酶复合体(RC)形成的重要调节蛋白分子;最新研究表明,SARS冠状病毒PLpro蛋白酶是一种病毒编码的去泛素化酶(DUB),对细胞蛋白具有明显去泛素化作用;而且对泛素(Ub)和泛素样分子ISG15均具有活性.PLpro蛋白酶对宿主抗病毒天然免疫反应具有负调节作用,是SARS冠状病毒的一种重要干扰素拮抗分子.PLpro蛋白酶是一种多功能病毒蛋白酶.本文结合作者课题组研究工作,对SARS冠状病毒PLpro蛋白酶结构和功能研究最新进展进行综述.

Severe acute respiratory syndrome（SARS） coronavirus genome encodes two viral proteases： a papain-like protease（PLpro） and a 3C-like protease（3CLpro）.PLpro has proteolytic activity in the cleavage and processing of N-terminals of replicase protein pp1a（pp1ab） to release the processed products of nonstructural proteins（nsp） 1 to nsp3,which plays an important regulatory role in assembling of SARS coronavirus functional replicase complex（RC） on intracellular membrane.Recent studies have revealed that SARS PLpro is a viral encoded deubiquitinase（DUB） enzyme capable of deubiquitinating cellular proteins in vivo.The DUB activity of PLpro is effective against both ubiquitin and the ubiquitin-like molecule,ISG15.PLpro is able to inhibit antiviral innate immunity response and therefore functions as interferon antagonist by blocking phosphorylation and activation of IRF-3,thereby antagonizing IFNβ induction.SARS-CoV PLpro is a multifunctional protease with nature of viral protease,DUB and IFN antagonist.This review will focus on recent progresses in our understanding of structure and functions of PLpro of SARS coronavirus.