4BH3

Haemagglutinin from a Transmissible Mutant H5 Influenza Virus in Complex with Human Receptor Analogue 6'-SLN

4BH3 の概要

• エントリーDOI: 10.2210/pdb4bh3/pdb
• 関連するPDBエントリー: 4BGW 4BGX 4BGY 4BGZ 4BH0 4BH1 4BH2 4BH4
• 関連するBIRD辞書のPRD_ID: PRD_900046
• 分子名称: HEMAGGLUTININ, beta-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, N-acetyl-alpha-neuraminic acid-(2-6)-beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• 機能のキーワード: viral protein, n-glycosylation, virus receptor, bird flu
• 由来する生物種: INFLUENZA VIRUS; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 58871.67

構造登録者

Xiong, X.,Coombs, P.J.,Martin, S.R.,Liu, J.,Xiao, H.,McCauley, J.W.,Locher, K.,Walker, P.A.,Collins, P.J.,Kawaoka, Y.,Skehel, J.J.,Gamblin, S.J. (登録日: 2013-03-29, 公開日: 2013-04-24, 最終更新日: 2024-10-09)

主引用文献

Xiong, X.,Coombs, P.J.,R Martin, S.,Liu, J.,Xiao, H.,Mccauley, J.W.,Locher, K.,Walker, P.A.,Collins, P.J.,Kawaoka, Y.,Skehel, J.J.,Gamblin, S.J.
Receptor Binding by a Ferret-Transmissible H5 Avian Influenza Virus
Nature, 497:392-, 2013

PubMed Abstract: Cell-surface-receptor binding by influenza viruses is a key determinant of their transmissibility, both from avian and animal species to humans as well as from human to human. Highly pathogenic avian H5N1 viruses that are a threat to public health have been observed to acquire affinity for human receptors, and transmissible-mutant-selection experiments have identified a virus that is transmissible in ferrets, the generally accepted experimental model for influenza in humans. Here, our quantitative biophysical measurements of the receptor-binding properties of haemagglutinin (HA) from the transmissible mutant indicate a small increase in affinity for human receptor and a marked decrease in affinity for avian receptor. From analysis of virus and HA binding data we have derived an algorithm that predicts virus avidity from the affinity of individual HA-receptor interactions. It reveals that the transmissible-mutant virus has a 200-fold preference for binding human over avian receptors. The crystal structure of the transmissible-mutant HA in complex with receptor analogues shows that it has acquired the ability to bind human receptor in the same folded-back conformation as seen for HA from the 1918, 1957 (ref. 4), 1968 (ref. 5) and 2009 (ref. 6) pandemic viruses. This binding mode is substantially different from that by which non-transmissible wild-type H5 virus HA binds human receptor. The structure of the complex also explains how the change in preference from avian to human receptors arises from the Gln226Leu substitution, which facilitates binding to human receptor but restricts binding to avian receptor. Both features probably contribute to the acquisition of transmissibility by this mutant virus.

PubMed: 23615615
DOI: 10.1038/NATURE12144

実験手法

X-RAY DIFFRACTION (2 Å)