Histidine protonation and the activation of viral fusion proteins

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

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

48 Citaten (Scopus)

Samenvatting

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).

Originele taal-2English
Pagina's (van-tot)43-45
Aantal pagina's3
TijdschriftBiochemical Society Transactions
Volume36
DOI's
StatusPublished - feb-2008

Citeer dit