Wu Nicholas C, Yuan Meng, Liu Hejun, Lee Chang-Chun D, Zhu Xueyong, Bangaru Sandhya, Torres Jonathan L, Caniels Tom G, Brouwer Philip J M, van Gils Marit J, Sanders Rogier W, Ward Andrew B, Wilson Ian A
bioRxiv. 2020 Jul 27:2020.07.26.222232. doi: 10.1101/2020.07.26.222232.
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编码的中和抗体通常在SARS-CoV-2感染期间产生，并靶向刺突（S）蛋白的受体结合域（RBD）。由于结合RBD时的结构限制（模式A），此类IGHV3-53抗体通常具有较短的互补决定区H3（CDR H3）。然而，一小部分针对RBD的IGHV3-53抗体含有较长的CDR H3。此处两种IGHV3-53中和抗体的晶体结构表明，较长的CDR H3可以以不同的结合模式（模式B）容纳。这两类IGHV3-53抗体均靶向ACE2受体结合位点，但接近角度和分子相互作用非常不同。总体而言，这些发现强调了IGHV3-53在这种针对SARS-CoV-2的常见抗体反应中的多功能性，其中保守的IGHV3-53种系编码特征可与非常不同的CDR H3长度和轻链相结合，用于SARS-CoV-2 RBD识别和病毒中和。
