4JTV

Crystal structure of 2009 pandemic influenza virus hemagglutinin complexed with human receptor analogue LSTc

Summary for 4JTV

• Entry DOI: 10.2210/pdb4jtv/pdb
• Related: 4JTX 4JU0 4JUG 4JUH 4JUJ
• Related PRD ID: PRD_900046
• Descriptor: Hemagglutinin, N-acetyl-alpha-neuraminic acid-(2-6)-beta-D-galactopyranose-(1-4)-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-(1-3)-beta-D-galactopyranose, ... (8 entities in total)
• Functional Keywords: virus attachment, membrane fusion, viral protein
• Biological source: Influenza A virus; More
• Total number of polymer chains: 12
• Total formula weight: 331658.74

Authors

Zhang, W.,Shi, Y.,Qi, J.,Gao, F.,Li, Q.,Fan, Z.,Yan, J.,Gao, G.F. (deposition date: 2013-03-24, release date: 2013-05-01, Last modification date: 2024-10-30)

Primary citation

Zhang, W.,Shi, Y.,Qi, J.,Gao, F.,Li, Q.,Fan, Z.,Yan, J.,Gao, G.F.
Molecular basis of the receptor binding specificity switch of the hemagglutinins from both the 1918 and 2009 pandemic influenza A viruses by a D225G substitution
J.Virol., 87:5949-5958, 2013

PubMed Abstract: Influenza A virus uses sialic acids as cell entry receptors, and there are two main receptor forms, α2,6 linkage or α2,3 linkage to galactose, that determine virus host ranges (mammalian or avian). The receptor binding hemagglutinins (HAs) of both 1918 and 2009 pandemic H1N1 (18H1 and 09H1, respectively) influenza A viruses preferentially bind to the human α2,6 linkage receptor. A single D225G mutation in both H1s switches receptor binding specificity from α2,6 linkage binding to dual receptor binding. However, the molecular basis for this specificity switch is not fully understood. Here, we show via H1-ligand complex structures that the D225G substitution results in a loss of a salt bridge between amino acids D225 and K222, enabling the key residue Q226 to interact with the avian receptor, thereby obtaining dual receptor binding. This is further confirmed by a D225E mutant that retains human receptor binding specificity with the salt bridge intact.

PubMed: 23514882
DOI: 10.1128/JVI.00545-13

Experimental method

X-RAY DIFFRACTION (2.997 Å)