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).
Skip Nav Destination
Article navigation
February 2008
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article|
January 22 2008
Histidine protonation and the activation of viral fusion proteins
Daniela S. Mueller;
Daniela S. Mueller
1
*Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747AG Groningen, The Netherlands
†School of Molecular and Microbial Sciences, University of Queensland, Brisbane, QLD 4072, Australia
1To whom correspondence should be addressed (email d.s.mueller@rug.nl).
Search for other works by this author on:
Thorsten Kampmann;
Thorsten Kampmann
‡Department of Theoretical and Computational Biophysics, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany
Search for other works by this author on:
Ragothaman Yennamalli;
Ragothaman Yennamalli
§Centre for Computational Biology and Bioinformatics, School of Information Technology, Jawaharlal Nehru University, New Delhi-110067, India
Search for other works by this author on:
Paul R. Young;
Paul R. Young
†School of Molecular and Microbial Sciences, University of Queensland, Brisbane, QLD 4072, Australia
∥Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia
Search for other works by this author on:
Bostjan Kobe;
Bostjan Kobe
†School of Molecular and Microbial Sciences, University of Queensland, Brisbane, QLD 4072, Australia
∥Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia
¶Special Research Centre for Functional and Applied Genomics, University of Queensland, Brisbane, QLD 4072, Australia
Search for other works by this author on:
Alan E. Mark
Alan E. Mark
*Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747AG Groningen, The Netherlands
†School of Molecular and Microbial Sciences, University of Queensland, Brisbane, QLD 4072, Australia
∥Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
September 14 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2008 Biochemical Society
2008
Biochem Soc Trans (2008) 36 (1): 43–45.
Article history
Received:
September 14 2007
Citation
Daniela S. Mueller, Thorsten Kampmann, Ragothaman Yennamalli, Paul R. Young, Bostjan Kobe, Alan E. Mark; Histidine protonation and the activation of viral fusion proteins. Biochem Soc Trans 1 February 2008; 36 (1): 43–45. doi: https://doi.org/10.1042/BST0360043
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.