6N8D

Crystal structure of GII.4 2002 norovirus P domain in complex with neutralizing human antibody A1431

6N8D の概要

• エントリーDOI: 10.2210/pdb6n8d/pdb
• 関連するPDBエントリー: 6N81
• 分子名称: Major capsid protein, A1431 Fab light chain, A1431 Fab heavy chain (3 entities in total)
• 機能のキーワード: norovirus, human antibody, fab, complex, neutralizing, immune system
• 由来する生物種: Norovirus Hu/GII.4/Farmington Hills/2004/USA; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 164775.61

構造登録者

Changela, A.,Verardi, R.,Kwong, P.D. (登録日: 2018-11-29, 公開日: 2019-06-19, 最終更新日: 2024-10-16)

主引用文献

Lindesmith, L.C.,McDaniel, J.R.,Changela, A.,Verardi, R.,Kerr, S.A.,Costantini, V.,Brewer-Jensen, P.D.,Mallory, M.L.,Voss, W.N.,Boutz, D.R.,Blazeck, J.J.,Ippolito, G.C.,Vinje, J.,Kwong, P.D.,Georgiou, G.,Baric, R.S.
Sera Antibody Repertoire Analyses Reveal Mechanisms of Broad and Pandemic Strain Neutralizing Responses after Human Norovirus Vaccination.
Immunity, 50:1530-1541.e8, 2019

PubMed Abstract: Rapidly evolving RNA viruses, such as the GII.4 strain of human norovirus (HuNoV), and their vaccines elicit complex serological responses associated with previous exposure. Specific correlates of protection, moreover, remain poorly understood. Here, we report the GII.4-serological antibody repertoire-pre- and post-vaccination-and select several antibody clonotypes for epitope and structural analysis. The humoral response was dominated by GII.4-specific antibodies that blocked ancestral strains or by antibodies that bound to divergent genotypes and did not block viral-entry-ligand interactions. However, one antibody, A1431, showed broad blockade toward tested GII.4 strains and neutralized the pandemic GII.P16-GII.4 Sydney strain. Structural mapping revealed conserved epitopes, which were occluded on the virion or partially exposed, allowing for broad blockade with neutralizing activity. Overall, our results provide high-resolution molecular information on humoral immune responses after HuNoV vaccination and demonstrate that infection-derived and vaccine-elicited antibodies can exhibit broad blockade and neutralization against this prevalent human pathogen.

PubMed: 31216462
DOI: 10.1016/j.immuni.2019.05.007

実験手法

X-RAY DIFFRACTION (3.1 Å)