Alternative splicing tends to avoid partial removals of protein-protein interaction sites

BMC Genomics

Research Article

Alessio Colantoni¹  Gabriele Ausiello¹  Fabrizio Ferrè¹  Manuela Helmer-Citterich¹  Valerio Bianchi²  Pier Federico Gherardini³  Gianpaolo Scalia Tomba⁴ 

[1] Centre for Molecular Bioinformatics, Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica snc, 00133, Rome, Italy;Centre for Molecular Bioinformatics, Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica snc, 00133, Rome, Italy;Center for Genomic Science of IIT@SEMM, Istituto Italiano di Tecnologia, via Adamello 16, 20139, Milan, Italy;Centre for Molecular Bioinformatics, Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica snc, 00133, Rome, Italy;Department of Microbiology & Immunology, Baxter Laboratory for Stem Cell Biology, Stanford University School of Medicine, Stanford, California, USA;Department of Mathematics, University of Rome Tor Vergata, Via della Ricerca Scientifica snc, 00133, Rome, Italy;

关键词: Alternative splicing;    Protein-protein interaction;    Hot spots;    Protein three-dimensional structure;    Disordered regions;   

DOI  :  10.1186/1471-2164-14-379

 received in 2012-12-16, accepted in 2013-06-03,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundAnecdotal evidence of the involvement of alternative splicing (AS) in the regulation of protein-protein interactions has been reported by several studies. AS events have been shown to significantly occur in regions where a protein interaction domain or a short linear motif is present. Several AS variants show partial or complete loss of interface residues, suggesting that AS can play a major role in the interaction regulation by selectively targeting the protein binding sites. In the present study we performed a statistical analysis of the alternative splicing of a non-redundant dataset of human protein-protein interfaces known at molecular level to determine the importance of this way of modulation of protein-protein interactions through AS.ResultsUsing a Cochran-Mantel-Haenszel chi-square test we demonstrated that the alternative splicing-mediated partial removal of both heterodimeric and homodimeric binding sites occurs at lower frequencies than expected, and this holds true even if we consider only those isoforms whose sequence is less different from that of the canonical protein and which therefore allow to selectively regulate functional regions of the protein. On the other hand, large removals of the binding site are not significantly prevented, possibly because they are associated to drastic structural changes of the protein. The observed protection of the binding sites from AS is not preferentially directed towards putative hot spot interface residues, and is widespread to all protein functional classes.ConclusionsOur findings indicate that protein-protein binding sites are generally protected from alternative splicing-mediated partial removals. However, some cases in which the binding site is selectively removed exist, and here we discuss one of them.

【 授权许可】

Unknown   
© Colantoni et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.