5VTY

Crystal structure of the A/Hong Kong/1/1968 (H3N2) influenza virus hemagglutinin G225Q/L226A mutant in complex with 3'-SLN

Summary for 5VTY

• Entry DOI: 10.2210/pdb5vty/pdb
• Related: 5VTQ 5VTR 5VTU 5VTV 5VTW 5VTX 5VTZ 5VU4
• Related PRD ID: PRD_900067
• Descriptor: Hemagglutinin HA1 chain, Hemagglutinin HA2 chain, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: influenza a virus, hemagglutinin, mutant, receptor binding, viral protein
• Biological source: Influenza A virus (strain A/Hong Kong/1/1968 H3N2); More
• Total number of polymer chains: 6
• Total formula weight: 172896.86

Authors

Wu, N.C.,Wilson, I.A. (deposition date: 2017-05-18, release date: 2017-06-28, Last modification date: 2023-10-04)

Primary citation

Wu, N.C.,Xie, J.,Zheng, T.,Nycholat, C.M.,Grande, G.,Paulson, J.C.,Lerner, R.A.,Wilson, I.A.
Diversity of Functionally Permissive Sequences in the Receptor-Binding Site of Influenza Hemagglutinin.
Cell Host Microbe, 21:742-753.e8, 2017

PubMed Abstract: Influenza A virus hemagglutinin (HA) initiates viral entry by engaging host receptor sialylated glycans via its receptor-binding site (RBS). The amino acid sequence of the RBS naturally varies across avian and human influenza virus subtypes and is also evolvable. However, functional sequence diversity in the RBS has not been fully explored. Here, we performed a large-scale mutational analysis of the RBS of A/WSN/33 (H1N1) and A/Hong Kong/1/1968 (H3N2) HAs. Many replication-competent mutants not yet observed in nature were identified, including some that could escape from an RBS-targeted broadly neutralizing antibody. This functional sequence diversity is made possible by pervasive epistasis in the RBS 220-loop and can be buffered by avidity in viral receptor binding. Overall, our study reveals that the HA RBS can accommodate a much greater range of sequence diversity than previously thought, which has significant implications for the complex evolutionary interrelationships between receptor specificity and immune escape.

PubMed: 28618270
DOI: 10.1016/j.chom.2017.05.011

Experimental method

X-RAY DIFFRACTION (2.36 Å)