Elastase-mediated activation of the severe acute respiratory syndrome coronavirus spike protein at discrete sites within the S2 domain.
Elastase-mediated activation of the severe acute respiratory syndrome coronavirus spike protein at discrete sites within the S2 domain.
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DOI：
10.1074/jbc.m110.103275
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发表时间：
2010-07-23
期刊：
影响因子：
--
通讯作者：
Whittaker GR
中科院分区：
文献类型：
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作者：
Belouzard S;Madu I;Whittaker GR
蛋白水解引发是控制由病毒糖蛋白介导的膜融合活化的常用方法。严重急性呼吸综合征冠状病毒刺突蛋白（SARS-CoV S）可被多种宿主细胞蛋白酶引发，其中蛋白水解切割发生在S1/S2边界处和邻近S2结构域中的融合肽处。在这里，我们研究了引发的SARS-CoV S弹性蛋白酶，并显示在S2结构域中的残基Thr 795的重要作用。在S2切割位点附近产生一系列丙氨酸突变体，目的是检查S2内弹性蛋白酶介导的切割。蛋白水解切割和融合激活都通过改变切割位点位置来调节。我们提出了一种新的机制，即SARS-CoV融合蛋白的功能可以通过蛋白水解引发位点的空间调控来控制，这对病毒的发病机制具有重要意义。
Proteolytic priming is a common method of controlling the activation of membrane fusion mediated by viral glycoproteins. The severe acute respiratory syndrome coronavirus spike protein (SARS-CoV S) can be primed by a variety of host cell proteases, with proteolytic cleavage occurring both as the S1/S2 boundary and adjacent to a fusion peptide in the S2 domain. Here, we studied the priming of SARS-CoV S by elastase and show an important role for residue Thr795 in the S2 domain. A series of alanine mutants were generated in the vicinity of the S2 cleavage site, with the goal of examining elastase-mediated cleavage within S2. Both proteolytic cleavage and fusion activation were modulated by altering the cleavage site position. We propose a novel mechanism whereby SARS-CoV fusion protein function can be controlled by spatial regulation of the proteolytic priming site, with important implications for viral pathogenesis.