4NCC

Neutralizing antibody to murine norovirus

4NCC の概要

• エントリーDOI: 10.2210/pdb4ncc/pdb
• 分子名称: Fab fragment light, Fab fragment heavy (3 entities in total)
• 機能のキーワード: immunoglobin, antibody, murine norovirus, immune system
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 93685.15

構造登録者

Smith, T.,Li, M. (登録日: 2013-10-24, 公開日: 2014-02-19, 最終更新日: 2024-10-30)

主引用文献

Kolawole, A.O.,Li, M.,Xia, C.,Fischer, A.E.,Giacobbi, N.S.,Rippinger, C.M.,Proescher, J.B.,Wu, S.K.,Bessling, S.L.,Gamez, M.,Yu, C.,Zhang, R.,Mehoke, T.S.,Pipas, J.M.,Wolfe, J.T.,Lin, J.S.,Feldman, A.B.,Smith, T.J.,Wobus, C.E.
Flexibility in surface-exposed loops in a virus capsid mediates escape from antibody neutralization.
J.Virol., 88:4543-4557, 2014

PubMed Abstract: New human norovirus strains emerge every 2 to 3 years, partly due to mutations in the viral capsid that allow escape from antibody neutralization and herd immunity. To understand how noroviruses evolve antibody resistance, we investigated the structural basis for the escape of murine norovirus (MNV) from antibody neutralization. To identify specific residues in the MNV-1 protruding (P) domain of the capsid that play a role in escape from the neutralizing monoclonal antibody (MAb) A6.2, 22 recombinant MNVs were generated with amino acid substitutions in the A'B' and E'F' loops. Six mutations in the E'F' loop (V378F, A382K, A382P, A382R, D385G, and L386F) mediated escape from MAb A6.2 neutralization. To elucidate underlying structural mechanisms for these results, the atomic structure of the A6.2 Fab was determined and fitted into the previously generated pseudoatomic model of the A6.2 Fab/MNV-1 virion complex. Previously, two distinct conformations, A and B, of the atomic structures of the MNV-1 P domain were identified due to flexibility in the two P domain loops. A superior stereochemical fit of the A6.2 Fab to the A conformation of the MNV P domain was observed. Structural analysis of our observed escape mutants indicates changes toward the less-preferred B conformation of the P domain. The shift in the structural equilibrium of the P domain toward the conformation with poor structural complementarity to the antibody strongly supports a unique mechanism for antibody escape that occurs via antigen flexibility instead of direct antibody-antigen binding.

PubMed: 24501415
DOI: 10.1128/JVI.03685-13

実験手法

X-RAY DIFFRACTION (2.49 Å)