4PY7

Crystal Structure of Fab 3.1

4PY7 の概要

• エントリーDOI: 10.2210/pdb4py7/pdb
• 関連するPDBエントリー: 4PY8
• 分子名称: antibody 3.1 heavy chain, antibody 3.1 light chain (2 entities in total)
• 機能のキーワード: immunoglobulin fab fragment, neutralizing antibody, hemagglutinin glycoproteins, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 93526.73

構造登録者

Dreyfus, C. (登録日: 2014-03-26, 公開日: 2014-05-21, 最終更新日: 2024-10-30)

主引用文献

Wyrzucki, A.,Dreyfus, C.,Kohler, I.,Steck, M.,Wilson, I.A.,Hangartner, L.
Alternative Recognition of the Conserved Stem Epitope in Influenza A Virus Hemagglutinin by a VH3-30-Encoded Heterosubtypic Antibody.
J.Virol., 88:7083-7092, 2014

PubMed Abstract: A human monoclonal heterosubtypic antibody, MAb 3.1, with its heavy chain encoded by VH3-30, was isolated using phage display with immobilized hemagglutinin (HA) from influenza virus A/Japan/305/1957(H2N2) as the target. Antibody 3.1 potently neutralizes influenza viruses from the H1a clade (i.e., H1, H2, H5, H6) but has little neutralizing activity against the H1b clade. Its crystal structure in complex with HA from a pandemic H1N1 influenza virus, A/South Carolina/1/1918(H1N1), revealed that like other heterosubtypic anti-influenza virus antibodies, MAb 3.1 contacts a hydrophobic groove in the HA stem, primarily using its heavy chain. However, in contrast to the closely related monoclonal antibody (Mab) FI6 that relies heavily on HCDR3 for binding, MAb 3.1 utilizes residues from HCDR1, HCDR3, and framework region 3 (FR3). Interestingly, HCDR1 of MAb 3.1 adopts an α-helical conformation and engages in hydrophobic interactions with the HA very similar to those of the de novo in silico-designed and affinity-matured synthetic protein HB36.3. These findings improve our understanding of the molecular requirements for binding to the conserved epitope in the stem of the HA protein and, therefore, aid the development of more universal influenza vaccines targeting these epitopes.

PubMed: 24719426
DOI: 10.1128/JVI.00178-14

実験手法

X-RAY DIFFRACTION (2.7 Å)