Homology modeling study toward identifying structural properties in the HA2 B-loop that would influence the HA1 receptor-binding site.

Abstract

Influenza hemagglutinin (HA) consists of a fibrous globular stem (HA2) inserted into the viral membrane supporting a globular head (HA1). HA1 receptor-binding has been hypothesized to be structurally correlated to the HA2 B-loop, however, this was never fully understood. Here, we elucidated the structural relationship between the HA2 B-loop and the HA1 receptor-binding site (RBS). Throughout this study, we analyzed 2486 H1N1 HA homology models obtained from human, swine and avian strains during 1976-2012. Quality of all homology models were verified before further analyses. We established that amino acid residue 882 is putatively strain-conserved and differs in the human (K882), swine (H882) and avian (N882) strains. Moreover, we observed that the amino acid at residue 882 and, similarly, its orientation has the potential to influence the HA1 RBS diameter measurements which we hypothesize may consequentially affect influenza H1N1 viral infectivity, immune escape, transmissibility, and evolution.

• Authors: Marni E Cueno, Kenichi Imai, Kazufumi Shimizu, Kuniyasu Ochiai
• Journal: Journal of molecular graphics & modelling (J Mol Graph Model) Vol. 44 Pg. 161-7 (Jul 2013) ISSN: 1873-4243 [Electronic] United States
• PMID: 23831996 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Amino Acids
• Hemagglutinin Glycoproteins, Influenza Virus
• Receptors, Virus

Topics

• Amino Acids (chemistry)
• Animals
• Binding Sites
• Hemagglutinin Glycoproteins, Influenza Virus (chemistry, metabolism)
• Humans
• Influenza A Virus, H1N1 Subtype
• Models, Molecular
• Molecular Docking Simulation
• Molecular Dynamics Simulation
• Protein Conformation
• Quantitative Structure-Activity Relationship
• Receptors, Virus (chemistry, metabolism)