| Autor: |
Nikhil K. Tulsian, Palur V. Raghuvamsi, Xinlei Qian, Gu Yue, Bhuvaneshwari D/O Shunmuganathan, Firdaus Samsudin, Wong Yee Hwa, Lin Jianqing, Kiren Purushotorman, Mary M. Kozma, Bei Wang, Julien Lescar, Cheng-I Wang, Ganesh S. Anand, Peter J. Bond, Paul A. MacAry |
| Rok vydání: |
2021 |
| Popis: |
Previous studies on the structural relationship between human antibodies and SARS-CoV-2 have focused on generating static snapshots of antibody complexes with the Spike trimer. However, antibody-antigen interactions are dynamic, with significant binding-induced allosteric effects on conformations of antibody and its target antigen. In this study, we employ hydrogen-deuterium exchange mass spectrometry, in vitro assays, and molecular dynamics simulations to investigate the allosteric perturbations linked to binding events between a group of human antibodies with differential functional activities, and the Spike trimer from SARS-CoV-2. Our investigations have revealed key dynamic features that define weakly or moderately neutralizing antibodies versus those with strong neutralizing activity. These results provide mechanistic insights into the functional modes of human antibodies against COVID-19, and provide a rationale for effective antiviral strategies.TeaserDifferent neutralizing antibodies induce site-specific allosteric effects across SARS-CoV-2 Spike protein |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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