7JIE

Structure of GII.4 P-domain in Complex with NORO-320 FAB

7JIE の概要

• エントリーDOI: 10.2210/pdb7jie/pdb
• 分子名称: VP1, IgA Fab Heavy Chain, IgA Fab Light Chain, ... (4 entities in total)
• 機能のキーワード: antibody, complex, viral capsid protein, neutralization, viral protein
• 由来する生物種: Norovirus Hu/GII.4/Sydney/NSW0514/2012/AU; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 166277.76

構造登録者

Salmen, W.,Hu, L.,Prasad, B. (登録日: 2020-07-23, 公開日: 2021-06-30, 最終更新日: 2024-10-23)

主引用文献

Alvarado, G.,Salmen, W.,Ettayebi, K.,Hu, L.,Sankaran, B.,Estes, M.K.,Venkataram Prasad, B.V.,Crowe Jr., J.E.
Broadly cross-reactive human antibodies that inhibit genogroup I and II noroviruses.
Nat Commun, 12:4320-4320, 2021

PubMed Abstract: The rational development of norovirus vaccine candidates requires a deep understanding of the antigenic diversity and mechanisms of neutralization of the virus. Here, we isolate and characterize a panel of broadly cross-reactive naturally occurring human monoclonal IgMs, IgAs and IgGs reactive with human norovirus (HuNoV) genogroup I or II (GI or GII). We note three binding patterns and identify monoclonal antibodies (mAbs) that neutralize at least one GI or GII HuNoV strain when using a histo-blood group antigen (HBGA) blocking assay. The HBGA blocking assay and a virus neutralization assay using human intestinal enteroids reveal that the GII-specific mAb NORO-320, mediates HBGA blocking and neutralization of multiple GII genotypes. The Fab form of NORO-320 neutralizes GII.4 infection more potently than the mAb, however, does not block HBGA binding. The crystal structure of NORO-320 Fab in complex with GII.4 P-domain shows that the antibody recognizes a highly conserved region in the P-domain distant from the HBGA binding site. Dynamic light scattering analysis of GII.4 virus-like particles with mAb NORO-320 shows severe aggregation, suggesting neutralization is by steric hindrance caused by multivalent cross-linking. Aggregation was not observed with the Fab form of NORO-320, suggesting that this clone also has additional inhibitory features.

PubMed: 34262046
DOI: 10.1038/s41467-021-24649-w

実験手法

X-RAY DIFFRACTION (2.254 Å)