The identification of short linear motif-mediated interfaces within the human interactome

Bioinformatics. 2012 Apr 1;28(7):976-82. doi: 10.1093/bioinformatics/bts072. Epub 2012 Feb 10.

Abstract

Motivation: Eukaryotic proteins are highly modular, containing multiple interaction interfaces that mediate binding to a network of regulators and effectors. Recent advances in high-throughput proteomics have rapidly expanded the number of known protein-protein interactions (PPIs); however, the molecular basis for the majority of these interactions remains to be elucidated. There has been a growing appreciation of the importance of a subset of these PPIs, namely those mediated by short linear motifs (SLiMs), particularly the canonical and ubiquitous SH2, SH3 and PDZ domain-binding motifs. However, these motif classes represent only a small fraction of known SLiMs and outside these examples little effort has been made, either bioinformatically or experimentally, to discover the full complement of motif instances.

Results: In this article, interaction data are analysed to identify and characterize an important subset of PPIs, those involving SLiMs binding to globular domains. To do this, we introduce iELM, a method to identify interactions mediated by SLiMs and add molecular details of the interaction interfaces to both interacting proteins. The method identifies SLiM-mediated interfaces from PPI data by searching for known SLiM-domain pairs. This approach was applied to the human interactome to identify a set of high-confidence putative SLiM-mediated PPIs.

Availability: iELM is freely available at http://elmint.embl.de

Contact: [email protected]

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computational Biology / methods*
  • Databases, Protein*
  • Humans
  • Markov Chains
  • Protein Binding
  • Protein Interaction Domains and Motifs*
  • Proteins / chemistry*
  • Proteins / metabolism
  • Software

Substances

  • Proteins