Determining functionally important amino acid residues of the E1 protein of Venezuelan equine encephalitis virus

Surendra S. Negi, Andrey A. Kolokoltsov, Catherine H. Schein, Robert A. Davey, Werner Braun

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

A new method for predicting interacting residues in protein complexes, InterProSurf, was applied to the E1 envelope protein of Venezuelan equine encephalitis (VEEV). Monomeric and trimeric models of VEEV-E1 were constructed with our MPACK program, using the crystal structure of the E1 protein of Semliki forest virus as a template. An alignment of the E1 sequences from representative alphavirus sequences was used to determine physical chemical property motifs (likely functional areas) with our PCPMer program. Information on residue variability, propensity to be in protein interfaces, and surface exposure on the model was combined to predict surface clusters likely to interact with other viral or cellular proteins. Mutagenesis of these clusters indicated that the predictions accurately detected areas crucial for virus infection. In addition to the fusion peptide area in domain 2, at least two other surface areas play an important role in virus infection. We propose that these may be sites of interaction between the E1-E1 and E1-E2 subdomains of the envelope proteins that are required to assemble the functional unit. The InterProSurf method is, thus, an important new tool for predicting viral protein interactions. These results can aid in the design of new vaccines against alphaviruses and other viruses.

Original languageEnglish (US)
Pages (from-to)921-929
Number of pages9
JournalJournal of Molecular Modeling
Volume12
Issue number6
DOIs
StatePublished - Sep 2006

Fingerprint

encephalitis
Venezuelan Equine Encephalitis Viruses
viruses
Viruses
amino acids
Amino acids
proteins
Proteins
Amino Acids
Alphavirus
Virus Diseases
Venezuelan Equine Encephalomyelitides
infectious diseases
Semliki forest virus
Sequence Alignment
envelopes
Viral Proteins
Mutagenesis
vaccines
mutagenesis

Keywords

  • Alpha virus
  • Envelope glycoprotein
  • Functional site prediction
  • Protein-protein interaction
  • Venezuelan equine encephalitis virus (VEEV)

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biophysics
  • Computer Science Applications
  • Computational Theory and Mathematics

Cite this

Determining functionally important amino acid residues of the E1 protein of Venezuelan equine encephalitis virus. / Negi, Surendra S.; Kolokoltsov, Andrey A.; Schein, Catherine H.; Davey, Robert A.; Braun, Werner.

In: Journal of Molecular Modeling, Vol. 12, No. 6, 09.2006, p. 921-929.

Research output: Contribution to journalArticle

Negi, Surendra S. ; Kolokoltsov, Andrey A. ; Schein, Catherine H. ; Davey, Robert A. ; Braun, Werner. / Determining functionally important amino acid residues of the E1 protein of Venezuelan equine encephalitis virus. In: Journal of Molecular Modeling. 2006 ; Vol. 12, No. 6. pp. 921-929.
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