The role of histidine residues in low-pH-mediated viral membrane fusion

Kampmann, Thorsten, Meuller, Daniela S., Mark, Alan E., Young, Paul R. and Kobe, Bostjan (2006) The role of histidine residues in low-pH-mediated viral membrane fusion. Structure, 14 10: 1481-1487. doi:10.1016/j.str.2006.07.011


Author Kampmann, Thorsten
Meuller, Daniela S.
Mark, Alan E.
Young, Paul R.
Kobe, Bostjan
Title The role of histidine residues in low-pH-mediated viral membrane fusion
Journal name Structure   Check publisher's open access policy
ISSN 0969-2126
Publication date 2006-01-01
Sub-type Article (original research)
DOI 10.1016/j.str.2006.07.011
Volume 14
Issue 10
Start page 1481
End page 1487
Total pages 7
Place of publication Cambridge
Publisher Cell Press
Collection year 2006
Language eng
Subject C1
250105 Structural Chemistry
780105 Biological sciences
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 11 (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.
Keyword Biochemistry & Molecular Biology
Biophysics
Cell Biology
Influenza-virus Hemagglutinin
Semliki-forest-virus
Borne Encephalitis-virus
Envelope Glycoprotein
Conformational-change
Crystal-structure
Receptor-binding
Protein-e
Resolution
Mechanism
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 19:23:23 EST