Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2.

Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2.
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DOI:
10.1038/sj.emboj.7600640
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发表时间:
2005-04-20
期刊:
影响因子:
11.4
通讯作者:
Farzan, M
Farzan, M
中科院分区:
生物学1区
文献类型:
--
作者:
Li, WH;Zhang, CS;Sui, JH;Kuhn, JH;Moore, MJ;Luo, SW;Wong, SK;Huang, IC;Xu, KM;Vasilieva, N;Murakami, A;He, YQ;Marasco, WA;Guan, Y;Choe, HY;Farzan, M

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人血管紧张素转换酶2(ACE 2)是SARS冠状病毒(SARS-CoV)的功能性受体。在这里,我们确定了SARS-CoV刺突(S)蛋白结合位点ACE 2。我们还比较了在2002-2003年SARS爆发期间分离的SARS-CoV的S蛋白,以及在2003-2004年爆发期间分离的SARS-CoV的S蛋白,以及来自棕榈果子狸的S蛋白,棕榈果子狸是在人类中发现的SARS-CoV的可能来源。所有三个S蛋白结合,并利用棕榈果子狸ACE 2有效,但后两个S蛋白利用人ACE 2的效率明显低于在早期的人类疫情期间获得的S蛋白。这些S蛋白的较低亲和力可以通过改变人类ACE 2的S蛋白结合位点内的特定残基来补充,或者通过改变2002-2003年爆发期间保守的S蛋白残基479和487来补充。总的来说,这些数据描述了SARS-CoV适应人类细胞的重要分子相互作用,并提供了对2002-2003年SARS流行严重程度的深入了解。
Human angiotensin-converting enzyme 2 (ACE2) is a functional receptor for SARS coronavirus (SARS-CoV). Here we identify the SARS-CoV spike (S)-protein-binding site on ACE2. We also compare S proteins of SARS-CoV isolated during the 2002–2003 SARS outbreak and during the much less severe 2003–2004 outbreak, and from palm civets, a possible source of SARS-CoV found in humans. All three S proteins bound to and utilized palm-civet ACE2 efficiently, but the latter two S proteins utilized human ACE2 markedly less efficiently than did the S protein obtained during the earlier human outbreak. The lower affinity of these S proteins could be complemented by altering specific residues within the S-protein-binding site of human ACE2 to those of civet ACE2, or by altering S-protein residues 479 and 487 to residues conserved during the 2002–2003 outbreak. Collectively, these data describe molecular interactions important to the adaptation of SARS-CoV to human cells, and provide insight into the severity of the 2002–2003 SARS epidemic.
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通讯作者: Ambrosino, DM