3QQI

Crystal structure of the HA1 receptor binding domain of H2 hemagglutinin

Summary for 3QQI

• Entry DOI: 10.2210/pdb3qqi/pdb
• Related: 3QQB 3QQE 3QQO
• Descriptor: Hemagglutinin, 2-acetamido-2-deoxy-beta-D-glucopyranose, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, ... (4 entities in total)
• Functional Keywords: viral envelope protein, hemagglutinin, viral fusion protein, viral protein
• Biological source: Influenza A virus
• Total number of polymer chains: 2
• Total formula weight: 50058.28

Authors

Xu, R.,Wilson, I.A. (deposition date: 2011-02-15, release date: 2011-03-09, Last modification date: 2024-10-16)

Primary citation

Xu, R.,Wilson, I.A.
Structural Characterization of an Early Fusion Intermediate of Influenza Virus Hemagglutinin.
J.Virol., 85:5172-5182, 2011

PubMed Abstract: The hemagglutinin (HA) envelope protein of influenza virus mediates viral entry through membrane fusion in the acidic environment of the endosome. Crystal structures of HA in pre- and postfusion states have laid the foundation for proposals for a general fusion mechanism for viral envelope proteins. The large-scale conformational rearrangement of HA at low pH is triggered by a loop-to-helix transition of an interhelical loop (B loop) within the fusion domain and is often referred to as the "spring-loaded" mechanism. Although the receptor-binding HA1 subunit is believed to act as a "clamp" to keep the B loop in its metastable prefusion state at neutral pH, the "pH sensors" that are responsible for the clamp release and the ensuing structural transitions have remained elusive. Here we identify a mutation in the HA2 fusion domain from the influenza virus H2 subtype that stabilizes the HA trimer in a prefusion-like state at and below fusogenic pH. Crystal structures of this putative early intermediate state reveal reorganization of ionic interactions at the HA1-HA2 interface at acidic pH and deformation of the HA1 membrane-distal domain. Along with neutralization of glutamate residues on the B loop, these changes cause a rotation of the B loop and solvent exposure of conserved phenylalanines, which are key residues at the trimer interface of the postfusion structure. Thus, our study reveals the possible initial structural event that leads to release of the B loop from its prefusion conformation, which is aided by unexpected structural changes within the membrane-distal HA1 domain at low pH.

PubMed: 21367895
DOI: 10.1128/JVI.02430-10

Experimental method

X-RAY DIFFRACTION (1.65 Å)