Histidine protonation and the activation of viral fusion proteins

Daniela S. Mueller*, Thorsten Kampmann, Ragothaman Yennamalli, Paul R. Young, Bostjan Kobe, Alan E. Mark

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

47 Citations (Scopus)


Many viral fusion proteins only become activated under mildly acidic condition (pH 4.5-6.5) close to the pK(a) 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 histicline 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 histicline 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 histicline switch hypothesis of Kampmann et al. (2006).

Original languageEnglish
Pages (from-to)43-45
Number of pages3
JournalBiochemical Society Transactions
Publication statusPublished - Feb-2008


  • dengue virus
  • envelope glycoprotein
  • flavivirus
  • influenza virus
  • membrane fusion
  • pH-dependent fusion
  • PH

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