+Search query
-Structure paper
Title | Structure of an influenza group 2-neutralizing antibody targeting the hemagglutinin stem supersite. |
---|---|
Journal, issue, pages | Structure, Vol. 30, Issue 7, Page 993-1003.e6, Year 2022 |
Publish date | Apr 19, 2022 |
Authors | Crystal Sao-Fong Cheung / Jason Gorman / Sarah F Andrews / Reda Rawi / Mateo Reveiz / Chen-Hsiang Shen / Yiran Wang / Darcy R Harris / Alexandra F Nazzari / Adam S Olia / Julie Raab / I-Ting Teng / Raffaello Verardi / Shuishu Wang / Yongping Yang / Gwo-Yu Chuang / Adrian B McDermott / Tongqing Zhou / Peter D Kwong / |
PubMed Abstract | Several influenza antibodies with broad group 2 neutralization have recently been isolated. Here, we analyze the structure, class, and binding of one of these antibodies from an H7N9 vaccine trial, ...Several influenza antibodies with broad group 2 neutralization have recently been isolated. Here, we analyze the structure, class, and binding of one of these antibodies from an H7N9 vaccine trial, 315-19-1D12. The cryo-EM structure of 315-19-1D12 Fab in complex with the hemagglutinin (HA) trimer revealed the antibody to recognize the helix A region of the HA stem, at the supersite of vulnerability recognized by group 1-specific and by cross-group-neutralizing antibodies. 315-19-1D12 was derived from HV1-2 and KV2-28 genes and appeared to form a new antibody class. Bioinformatic analysis indicated its group 2 neutralization specificity to be a consequence of four key residue positions. We specifically tested the impact of the group 1-specific N33 glycan, which decreased but did not abolish group 2 binding of 315-19-1D12. Overall, this study highlights the recognition of a broad group 2-neutralizing antibody, revealing unexpected diversity in neutralization specificity for antibodies that recognize the HA stem supersite. |
External links | Structure / PubMed:35489332 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.76 Å |
Structure data | EMDB-21961, PDB-6wxl: |
Chemicals | ChemComp-NAG: |
Source |
|
Keywords | IMMUNE SYSTEM / VRC / VRC315 / Group 2 / Fab |