8UT4

CryoEM structure of A/Michigan/45/2015 H1 in complex with flu HA central stem VH1-18 antibody 09-1B12

8UT4 の概要

• エントリーDOI: 10.2210/pdb8ut4/pdb
• EMDBエントリー: 42529
• 分子名称: Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, 09-1B12 HC Fv, ... (5 entities in total)
• 機能のキーワード: flu hemagglutinin, central stem epitope, vh1-18, viral protein, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Influenza A virus; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 223204.77

構造登録者

Huang, J.,Han, J.,Ward, A.B. (登録日: 2023-10-30, 公開日: 2024-05-08, 最終更新日: 2024-10-23)

主引用文献

Ray, R.,Nait Mohamed, F.A.,Maurer, D.P.,Huang, J.,Alpay, B.A.,Ronsard, L.,Xie, Z.,Han, J.,Fernandez-Quintero, M.,Phan, Q.A.,Ursin, R.L.,Vu, M.,Kirsch, K.H.,Prum, T.,Rosado, V.C.,Bracamonte-Moreno, T.,Okonkwo, V.,Bals, J.,McCarthy, C.,Nair, U.,Kanekiyo, M.,Ward, A.B.,Schmidt, A.G.,Batista, F.D.,Lingwood, D.
Eliciting a single amino acid change by vaccination generates antibody protection against group 1 and group 2 influenza A viruses.
Immunity, 57:1141-1159.e11, 2024

PubMed Abstract: Broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem of influenza A viruses (IAVs) tend to be effective against either group 1 or group 2 viral diversity. In rarer cases, intergroup protective bnAbs can be generated by human antibody paratopes that accommodate the conserved glycan differences between the group 1 and group 2 stems. We applied germline-engaging nanoparticle immunogens to elicit a class of cross-group bnAbs from physiological precursor frequency within a humanized mouse model. Cross-group protection depended on the presence of the human bnAb precursors within the B cell repertoire, and the vaccine-expanded antibodies enriched for an N55T substitution in the CDRH2 loop, a hallmark of the bnAb class. Structurally, this single mutation introduced a flexible fulcrum to accommodate glycosylation differences and could alone enable cross-group protection. Thus, broad IAV immunity can be expanded from the germline repertoire via minimal antigenic input and an exceptionally simple antibody development pathway.

PubMed: 38670113
DOI: 10.1016/j.immuni.2024.03.022

実験手法

ELECTRON MICROSCOPY (3.3 Å)