An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain.
An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain.
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DOI：
10.1101/2020.07.26.222232
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发表时间：
2020-10-20
期刊：
影响因子：
8.8
通讯作者：
Wilson, Ian A
中科院分区：
文献类型：
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作者：
Wu, Nicholas C;Yuan, Meng;Wilson, Ian A
ighv3 -53编码的中和抗体通常在SARS-CoV-2感染期间被激发，并靶向刺突(S)蛋白的受体结合域（RBD）。由于结合RBD的结构限制，这类IGHV3-53抗体通常具有较短的CDR H3（模式a）。然而，一小部分针对RBD的IGHV3-53抗体含有更长的CDR H3。两种IGHV3-53中和抗体的晶体结构表明，更长的CDR H3可以适应不同的结合模式（模式B）。这两类IGHV3-53抗体都靶向ACE2受体结合位点，但途径角度和分子相互作用非常不同。总的来说，这些发现强调了IGHV3-53在这种针对SARS-CoV-2的常见抗体应答中的多功能性，其中保守的IGHV3-53种系编码特征可以与非常不同的CDR H3长度和轻链结合，用于SARS-CoV-2 RBD识别和病毒中和。ighv3 -53编码的中和抗体通常在SARS-CoV-2感染期间被激发，并靶向刺突(S)蛋白的受体结合域（RBD）。由于结合RBD的结构限制，这类IGHV3-53抗体通常具有较短的CDR H3（模式a）。然而，一小部分针对RBD的IGHV3-53抗体含有更长的CDR H3。两种IGHV3-53中和抗体的晶体结构表明，更长的CDR H3可以适应不同的结合模式（模式B）。这两类IGHV3-53抗体都靶向ACE2受体结合位点，但途径角度和分子相互作用非常不同。总的来说，这些发现强调了IGHV3-53在这种针对SARS-CoV-2的常见抗体应答中的多功能性，其中保守的IGHV3-53种系编码特征可以与非常不同的CDR H3长度和轻链结合，用于SARS-CoV-2 RBD识别和病毒中和。
IGHV3-53-encoded neutralizing antibodies are commonly elicited during SARS-CoV-2 infection and target the receptor-binding domain (RBD) of the spike (S) protein. Such IGHV3-53 antibodies generally have a short CDR H3 due to structural constraints in binding the RBD (mode A). However, a small subset of IGHV3-53 antibodies to the RBD contain a longer CDR H3. Crystal structures of two IGHV3-53 neutralizing antibodies here demonstrate that a longer CDR H3 can be accommodated in a different binding mode (mode B). These two classes of IGHV3-53 antibodies both target the ACE2 receptor binding site, but with very different angles of approach and molecular interactions. Overall, these findings emphasize the versatility of IGHV3-53 in this common antibody response to SARS-CoV-2, where conserved IGHV3-53 germline-encoded features can be combined with very different CDR H3 lengths and light chains for SARS-CoV-2 RBD recognition and virus neutralization.IGHV3-53-encoded neutralizing antibodies are commonly elicited during SARS-CoV-2 infection and target the receptor-binding domain (RBD) of the spike (S) protein. Such IGHV3-53 antibodies generally have a short CDR H3 because of structural constraints in binding the RBD (mode A). However, a small subset of IGHV3-53 antibodies to the RBD contain a longer CDR H3. Crystal structures of two IGHV3-53 neutralizing antibodies here demonstrate that a longer CDR H3 can be accommodated in a different binding mode (mode B). These two classes of IGHV3-53 antibodies both target the ACE2 receptor binding site, but with very different angles of approach and molecular interactions. Overall, these findings emphasize the versatility of IGHV3-53 in this common antibody response to SARS-CoV-2, where conserved IGHV3-53 germline-encoded features can be combined with very different CDR H3 lengths and light chains for SARS-CoV-2 RBD recognition and virus neutralization.