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Sequence- and interactome-based prediction of viral protein hotspots targeting host proteins: a case study for HIV Nef.
- Source :
-
PloS one [PLoS One] 2011; Vol. 6 (6), pp. e20735. Date of Electronic Publication: 2011 Jun 28. - Publication Year :
- 2011
-
Abstract
- Virus proteins alter protein pathways of the host toward the synthesis of viral particles by breaking and making edges via binding to host proteins. In this study, we developed a computational approach to predict viral sequence hotspots for binding to host proteins based on sequences of viral and host proteins and literature-curated virus-host protein interactome data. We use a motif discovery algorithm repeatedly on collections of sequences of viral proteins and immediate binding partners of their host targets and choose only those motifs that are conserved on viral sequences and highly statistically enriched among binding partners of virus protein targeted host proteins. Our results match experimental data on binding sites of Nef to host proteins such as MAPK1, VAV1, LCK, HCK, HLA-A, CD4, FYN, and GNB2L1 with high statistical significance but is a poor predictor of Nef binding sites on highly flexible, hoop-like regions. Predicted hotspots recapture CD8 cell epitopes of HIV Nef highlighting their importance in modulating virus-host interactions. Host proteins potentially targeted or outcompeted by Nef appear crowding the T cell receptor, natural killer cell mediated cytotoxicity, and neurotrophin signaling pathways. Scanning of HIV Nef motifs on multiple alignments of hepatitis C protein NS5A produces results consistent with literature, indicating the potential value of the hotspot discovery in advancing our understanding of virus-host crosstalk.
- Subjects :
- Amino Acid Motifs
Amino Acid Sequence
CD4 Antigens chemistry
CD4 Antigens metabolism
GTP-Binding Proteins chemistry
GTP-Binding Proteins metabolism
HLA-A Antigens chemistry
HLA-A Antigens metabolism
Humans
Mitogen-Activated Protein Kinase 1 chemistry
Mitogen-Activated Protein Kinase 1 metabolism
Molecular Sequence Data
Neoplasm Proteins chemistry
Neoplasm Proteins metabolism
Protein Binding
Proto-Oncogene Proteins c-fyn chemistry
Proto-Oncogene Proteins c-fyn metabolism
Proto-Oncogene Proteins c-hck chemistry
Proto-Oncogene Proteins c-hck metabolism
Proto-Oncogene Proteins c-vav chemistry
Proto-Oncogene Proteins c-vav metabolism
Receptors for Activated C Kinase
Receptors, Cell Surface chemistry
Receptors, Cell Surface metabolism
Computational Biology methods
nef Gene Products, Human Immunodeficiency Virus chemistry
nef Gene Products, Human Immunodeficiency Virus metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 6
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 21738584
- Full Text :
- https://doi.org/10.1371/journal.pone.0020735