Histidine protonation and the activation of viral fusion proteins

Mueller, D., Kampmann, T., Yennamalli, R., Young, P.R., Kobe, B. and Mark, A. E. (2008) Histidine protonation and the activation of viral fusion proteins. Biochemical Society Transactions, 36 1: 43-45. doi:10.1042/BST0360043


Author Mueller, D.
Kampmann, T.
Yennamalli, R.
Young, P.R.
Kobe, B.
Mark, A. E.
Title Histidine protonation and the activation of viral fusion proteins
Journal name Biochemical Society Transactions   Check publisher's open access policy
ISSN 0300-5127
Publication date 2008-01-01
Sub-type Article (original research)
DOI 10.1042/BST0360043
Volume 36
Issue 1
Start page 43
End page 45
Total pages 3
Editor Richardson, D.
Place of publication United Kingdom
Publisher Portland Press Ltd
Collection year 2009
Language eng
Subject C1
060506 Virology
110309 Infectious Diseases
970106 Expanding Knowledge in the Biological Sciences
920412 Preventive Medicine
Abstract Many viral fusion proteins only become activated under mildly acidic condition (pH 4.5–6.5) close to the pKa of histidine side-chain protonation. Analysis of the sequences and structures of influenza HA (haemagglutinin) and flaviviral envelope glycoproteins has led to the identification of a number of histidine residues that are not only fully conserved themselves but have local environments that are also highly conserved [Kampmann, Mueller, Mark, Young and Kobe (2006) Structure 14, 1481–1487]. Here, we summarize studies aimed at determining the role, if any, that protonation of these potential switch histidine residues plays in the low-pH-dependent conformational changes associated with fusion activation of a flaviviral envelope protein. Specifically, we report on MD (Molecular Dynamics) simulations of the DEN2 (dengue virus type 2) envelope protein ectodomain sE (soluble E) performed under varied pH conditions designed to test the histidine switch hypothesis of Kampmann et al. (2006).
Keyword dengue virus
envelope glycoprotein
flavivirus
influenza virus
membrane fusion
pH-dependent fusion
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Chemistry and Molecular Biosciences
 
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Created: Sat, 07 Mar 2009, 01:45:28 EST by Jennifer Falknau on behalf of School of Chemistry & Molecular Biosciences