TY - JOUR
T1 - Identification of Semaphorin 5A Interacting Protein by Applying Apriori Knowledge and Peptide Complementarity Related to Protein Evolution and Structure
AU - Sadanandam, Anguraj
AU - Varney, Michelle L.
AU - Singh, Rakesh K.
N1 - Funding Information:
This work was partly supported by Molecular Therapeutics Program, Nebraska Department of Health and Human Services and by Grant CA72781 (to RKS) and Cancer Center Support Grant ( P30CA036727 ) from National Cancer Institute, National Institutes of Health, USA.
PY - 2008
Y1 - 2008
N2 - In the post-genomic era, various computational methods that predict protein-protein interactions at the genome level are available; however, each method has its own advantages and disadvantages, resulting in false predictions. Here we developed a unique integrated approach to identify interacting partner(s) of Semaphorin 5A (SEMA5A), beginning with seven proteins sharing similar ligand interacting residues as putative binding partners. The methods include Dwyer and Root-Bernstein/Dillon theories of protein evolution, hydropathic complementarity of protein structure, pattern of protein functions among molecules, information on domain-domain interactions, co-expression of genes and protein evolution. Among the set of seven proteins selected as putative SEMA5A interacting partners, we found the functions of Plexin B3 and Neuropilin-2 to be associated with SEMA5A. We modeled the semaphorin domain structure of Plexin B3 and found that it shares similarity with SEMA5A. Moreover, a virtual expression database search and RT-PCR analysis showed co-expression of SEMA5A and Plexin B3 and these proteins were found to have co-evolved. In addition, we confirmed the interaction of SEMA5A with Plexin B3 in co-immunoprecipitation studies. Overall, these studies demonstrate that an integrated method of prediction can be used at the genome level for discovering many unknown protein binding partners with known ligand binding domains.
AB - In the post-genomic era, various computational methods that predict protein-protein interactions at the genome level are available; however, each method has its own advantages and disadvantages, resulting in false predictions. Here we developed a unique integrated approach to identify interacting partner(s) of Semaphorin 5A (SEMA5A), beginning with seven proteins sharing similar ligand interacting residues as putative binding partners. The methods include Dwyer and Root-Bernstein/Dillon theories of protein evolution, hydropathic complementarity of protein structure, pattern of protein functions among molecules, information on domain-domain interactions, co-expression of genes and protein evolution. Among the set of seven proteins selected as putative SEMA5A interacting partners, we found the functions of Plexin B3 and Neuropilin-2 to be associated with SEMA5A. We modeled the semaphorin domain structure of Plexin B3 and found that it shares similarity with SEMA5A. Moreover, a virtual expression database search and RT-PCR analysis showed co-expression of SEMA5A and Plexin B3 and these proteins were found to have co-evolved. In addition, we confirmed the interaction of SEMA5A with Plexin B3 in co-immunoprecipitation studies. Overall, these studies demonstrate that an integrated method of prediction can be used at the genome level for discovering many unknown protein binding partners with known ligand binding domains.
KW - domain-domain interaction
KW - plexin
KW - protein interaction prediction
KW - semaphorin
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U2 - 10.1016/S1672-0229(09)60004-8
DO - 10.1016/S1672-0229(09)60004-8
M3 - Article
C2 - 19329067
AN - SCOPUS:62949084182
SN - 1672-0229
VL - 6
SP - 163
EP - 174
JO - Genomics, Proteomics and Bioinformatics
JF - Genomics, Proteomics and Bioinformatics
IS - 3-4
ER -