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


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


BACKGROUND
toby.gibson@embl.de


BACKGROUND
Supplementary data are available at Bioinformatics online.
Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
R J
RJ
Weatheritt
K
K
Luck
E
E
Petsalaki
N E
NE
Davey
T J
TJ
Gibson
D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D006801:Humans; D008390:Markov Chains; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D012984:Software
D011506:Proteins