Identification of Semaphorin 5A Interacting Protein by Applying Apriori Knowledge and Peptide Complementarity Related to Protein Evolution and Structure

Anguraj Sadanandam, Michelle L. Varney, Rakesh K. Singh

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)163-174
Number of pages12
JournalGenomics, Proteomics and Bioinformatics
Volume6
Issue number3-4
DOIs
StatePublished - 2008

Keywords

  • domain-domain interaction
  • plexin
  • protein interaction prediction
  • semaphorin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Computational Mathematics

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