The molecular basis for SARS-CoV-2 binding to dog ACE2.

The molecular basis for SARS-CoV-2 binding to dog ACE2.
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SARS-CoV-2 与狗 ACE2 结合的分子基础

DOI:
10.1038/s41467-021-24326-y
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发表时间:
2021-07-07
影响因子:
16.6
通讯作者:
Sun Y
Sun Y
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Zhang Z;Zhang Y;Liu K;Li Y;Lu Q;Wang Q;Zhang Y;Wang L;Liao H;Zheng A;Ma S;Fan Z;Li H;Huang W;Bi Y;Zhao X;Wang Q;Gao GF;Xiao H;Tong Z;Qi J;Sun Y

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SARS-CoV-2可以感染许多家畜,包括狗。在此,我们表明狗血管紧张素转换酶2(dACE 2)可以结合到SARS-CoV-2刺突(S)蛋白受体结合域(RBD),假型和真实的SARS-CoV-2可以感染dACE 2表达细胞。我们解析了RBD与dACE 2复合物的晶体结构,发现该复合物中结合界面的接触残基、接触原子、氢键和盐桥的总数略少于RBD与人ACE 2(hACE 2)复合物中的接触残基、接触原子、氢键和盐桥的总数。该结果与RBD与dACE 2的结合亲和力低于hACE 2的结合亲和力的事实一致。我们进一步表明,在RBD结合界面中的一些重要突变在RBD与dACE 2和hACE 2的结合亲和力中起着关键作用。我们的工作揭示了SARS-CoV-2跨物种传播和潜在动物传播的分子基础,并为阻断该病毒的潜在传播链提供了新的线索。
SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. We solved the crystal structure of RBD in complex with dACE2 and found that the total number of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that of hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2. Our work reveals a molecular basis for cross-species transmission and potential animal spread of SARS-CoV-2, and provides new clues to block the potential transmission chains of this virus.
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