title: The Role of histidine residues in low-pH-mediated viral membrane fusion.
abstract: A central event in the invasion of a host cell by an enveloped virus is the fusion of viral and cell membranes. For many viruses, membrane fusion is driven by specific viral surface proteins that undergo large-scale conformational rearrangements, triggered by exposure to low pH in the endosome upon internalization. Here, we present evidence suggesting that in both class I (helical hairpin proteins) and class II (beta-structure-rich proteins) pH-dependent fusion proteins the protonation of specific histidine residues triggers fusion via an analogous molecular mechanism. These histidines are located in the vicinity of positively charged residues in the prefusion conformation, and they subsequently form salt bridges with negatively charged residues in the postfusion conformation. The molecular surfaces involved in the corresponding structural rearrangements leading to fusion are highly conserved and thus might provide a suitable common target for the design of antivirals, which could be active against a diverse range of pathogenic viruses.
authors.affiliation: School of Molecular and Microbial Sciences, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Kampmann
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Mueller
authors.forename: Alan E
authors.initials: AE
authors.lastname: Mark
authors.forename: Paul R
authors.initials: PR
authors.lastname: Young
authors.forename: Bostjan
authors.initials: B
authors.lastname: Kobe
mesh_terms: D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000502:physiology*; D006639:Histidine / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008561:Membrane Fusion / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D014760:Viral Fusion Proteins / Q000737:chemistry / Q000502:physiology*
chemical_list: D014760:Viral Fusion Proteins; D006639:Histidine