5E35

Crystal structure of H5 hemagglutinin mutant (N224K, Q226L, N158D and L133a deletion) from the influenza virus A/chicken/Vietnam/NCVD-093/2008 (H5N1) with LSTc

Summary for 5E35

• Entry DOI: 10.2210/pdb5e35/pdb
• Related: 5E2Y 5E2Z 5E30 5E32 5E34
• 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, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: h5n1 influenza virus, hemagglutinin, receptor binding specificity, transmission, glycan complex, viral protein
• Biological source: Influenza A virus (A/chicken/Vietnam/NCVD-093/2008(H5N1)); More
• Total number of polymer chains: 2
• Total formula weight: 59573.86

Authors

Zhu, X.,Wilson, I.A. (deposition date: 2015-10-01, release date: 2015-12-02, Last modification date: 2024-10-23)

Primary citation

Zhu, X.,Viswanathan, K.,Raman, R.,Yu, W.,Sasisekharan, R.,Wilson, I.A.
Structural Basis for a Switch in Receptor Binding Specificity of Two H5N1 Hemagglutinin Mutants.
Cell Rep, 13:1683-1691, 2015

PubMed Abstract: Avian H5N1 influenza viruses continue to spread in wild birds and domestic poultry with sporadic infection in humans. Receptor binding specificity changes are a prerequisite for H5N1 viruses and other zoonotic viruses to be transmitted among humans. Previous reported hemagglutinin (HA) mutants from ferret-transmissible H5N1 viruses of A/Vietnam/1203/2004 and A/Indonesia/5/2005 showed slightly increased, but still very weak, binding to human receptors. From mutagenesis and glycan array studies, we previously identified two H5N1 HA mutants that could more effectively switch receptor specificity to human-like α2-6-linked sialosides with avidity comparable to wild-type H5 HA binding to avian-like α2-3-linked sialosides. Here, crystal structures of these two H5 HA mutants free and in complex with human and avian glycan receptor analogs reveal the structural basis for their preferential binding to human receptors. These findings suggest continuous surveillance should be maintained to monitor and assess human-to-human transmission potential of H5N1 viruses.

PubMed: 26586437
DOI: 10.1016/j.celrep.2015.10.027

Experimental method

X-RAY DIFFRACTION (2.7 Å)