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 language | English (US) |
|---|---|
| Pages (from-to) | 921-929 |
| Number of pages | 9 |
| Journal | Journal of Molecular Modeling |
| Volume | 12 |
| Issue number | 6 |
| DOIs | |
| State | Published - Sep 2006 |
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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 journal › Article
}
TY - JOUR
T1 - Determining functionally important amino acid residues of the E1 protein of Venezuelan equine encephalitis virus
AU - Negi, Surendra S.
AU - Kolokoltsov, Andrey A.
AU - Schein, Catherine H.
AU - Davey, Robert A.
AU - Braun, Werner
PY - 2006/9
Y1 - 2006/9
N2 - 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.
AB - 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.
KW - Alpha virus
KW - Envelope glycoprotein
KW - Functional site prediction
KW - Protein-protein interaction
KW - Venezuelan equine encephalitis virus (VEEV)
UR - http://www.scopus.com/inward/record.url?scp=33749252782&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33749252782&partnerID=8YFLogxK
U2 - 10.1007/s00894-006-0101-7
DO - 10.1007/s00894-006-0101-7
M3 - Article
C2 - 16607494
AN - SCOPUS:33749252782
VL - 12
SP - 921
EP - 929
JO - Journal of Molecular Modeling
JF - Journal of Molecular Modeling
SN - 1610-2940
IS - 6
ER -