6S0Y

Nanobody targeting influenza A matrix protein 2 ectodomain (M2e)

6S0Y の概要

• エントリーDOI: 10.2210/pdb6s0y/pdb
• 分子名称: M2e-VHH-23m, Matrix protein 2 (3 entities in total)
• 機能のキーワード: influenza a, fc gamma receptor iv, m2 matrix protein, nanobody, antiviral protein
• 由来する生物種: Lama glama; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 31629.21

構造登録者

Van Molle, I.,De Vlieger, D.,Schepens, B.,Remaut, H.,Saelens, X. (登録日: 2019-06-18, 公開日: 2020-01-22, 最終更新日: 2024-10-09)

主引用文献

De Vlieger, D.,Hoffmann, K.,Van Molle, I.,Nerinckx, W.,Van Hoecke, L.,Ballegeer, M.,Creytens, S.,Remaut, H.,Hengel, H.,Schepens, B.,Saelens, X.
Selective Engagement of Fc gamma RIV by a M2e-Specific Single Domain Antibody Construct Protects Against Influenza A Virus Infection.
Front Immunol, 10:2920-2920, 2019

PubMed Abstract: Lower respiratory tract infections, such as infections caused by influenza A viruses, are a constant threat for public health. Antivirals are indispensable to control disease caused by epidemic as well as pandemic influenza A. We developed a novel anti-influenza A virus approach based on an engineered single-domain antibody (VHH) construct that can selectively recruit innate immune cells to the sites of virus replication. This protective construct comprises two VHHs. One VHH binds with nanomolar affinity to the conserved influenza A matrix protein 2 (M2) ectodomain (M2e). Co-crystal structure analysis revealed that the complementarity determining regions 2 and 3 of this VHH embrace M2e. The second selected VHH specifically binds to the mouse Fcγ Receptor IV (FcγRIV) and was genetically fused to the M2e-specific VHH, which resulted in a bi-specific VHH-based construct that could be efficiently expressed in . In the presence of M2 expressing or influenza A virus-infected target cells, this single domain antibody construct selectively activated the mouse FcγRIV. Moreover, intranasal delivery of this bispecific FcγRIV-engaging VHH construct protected wild type but not γ mice against challenge with an H3N2 influenza virus. These results provide proof of concept that VHHs directed against a surface exposed viral antigen can be readily armed with effector functions that trigger protective antiviral activity beyond direct virus neutralization.

PubMed: 31921179
DOI: 10.3389/fimmu.2019.02920

実験手法

X-RAY DIFFRACTION (1.81 Å)