Golestan University of Medical Sciences Repository

Characterizing a histidine switch controlling ph-dependent conformational changes of the influenza virus hemagglutinin

Kalani, M.R. and Moradi, A. and Moradi, M. and Tajkhorshid, E. (2013) Characterizing a histidine switch controlling ph-dependent conformational changes of the influenza virus hemagglutinin. Biophysical Journal, 105 (4). pp. 993-1003. ISSN 00063495 (ISSN)

[img] PDF - Published Version
Restricted to Repository staff only

Download (3MB)


During the fusion of the influenza virus to the host cell, bending of the HA2 chain of hemagglutinin into a hairpin-shaped structure in a pH-dependent manner facilitates the fusion of the viral envelope and the endosomal membrane. To characterize the structural and dynamical responses of the hinge region of HA2 to pH changes and examine the role of a conserved histidine in this region (the hinge histidine), we have performed an extensive set of molecular dynamics (MD) simulations of 26-residue peptides encompassing the hinge regions of several hemagglutinin subtypes under both neutral and low pH conditions, modeled by the change of the protonation state of the hinge histidine. More than 70 sets of MD simulations (collectively amounting to 25.1 μs) were performed in both implicit and explicit solvents to study the effect of histidine protonation on structural dynamics of the hinge region. In both explicit and implicit solvent simulations, hinge bending was consistently observed upon the protonation of the histidine in all the simulations starting with an initial straight helical conformation, whereas the systems with a neutral histidine retained their primarily straight conformation throughout the simulations. Conversely, the MD simulations starting from an initially bent conformation resulted in the formation of a straight helical structure upon the neutralization of the hinge histidine, whereas the bent structure was maintained when the hinge histidine remained protonated. Finally, mutation of the hinge histidine to alanine abolishes the bending response of the peptide altogether. A molecular mechanism based on the interaction of the hinge histidine with neighboring acidic residues is proposed to be responsible for its role in controlling the conformation of the hinge. We propose that this might present a common mechanism for pH-controlled structural changes in helical structures when histidines act as the pH sensor. © 2013 Biophysical Society.

Item Type: Article
Additional Information: Unmapped bibliographic data: LA - English [Field not mapped to EPrints] J2 - Biophys. J. [Field not mapped to EPrints] C2 - 23972851 [Field not mapped to EPrints] AD - Department of Biochemistry, College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, United States [Field not mapped to EPrints] AD - Faculty of Advanced Medical Technology, Golestan University of Medical Sciences, Gorgan, Iran [Field not mapped to EPrints] DB - Scopus [Field not mapped to EPrints]
Uncontrolled Keywords: histidine, Influenza virus hemagglutinin, peptide fragment, article, chemistry, genetics, Influenza virus A, molecular dynamics, mutation, pH, protein secondary structure, Hemagglutinin Glycoproteins, Influenza Virus, Histidine, Hydrogen-Ion Concentration, Influenza A virus, Molecular Dynamics Simulation, Mutation, Peptide Fragments, Protein Structure, Secondary
Subjects: مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
موارد کلی
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 15 Apr 2015 10:03
Last Modified: 26 Feb 2018 06:26
URI: http://eprints.goums.ac.ir/id/eprint/1841

Actions (login required)

View Item View Item