SLiM on diet: Finding short linear motifs on domain interaction interfaces in protein data bank

Willy Hugo, Fushan Song, Zeyar Aung, See Kiong Ng, Wing Kin Sung

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Motivation: An important class of protein interactions involves the binding of a protein's domain to a short linear motif (SLiM) on its interacting partner. Extracting such motifs, either experimentally or computationally, is challenging because of their weak binding and high degree of degeneracy. Recent rapid increase of available protein structures provides an excellent opportunity to study SLiMs directly from their 3D structures. Results: Using domain interface extraction (Diet), we characterized 452 distinct SLiMs from the Protein Data Bank (PDB), of which 155 are validated in varying degrees-40 have literature validation, 54 are supported by at least one domain-peptide structural instance, and another 61 have overrepresentation in high-throughput PPI data. We further observed that the lacklustre coverage of existing computational SLiM detection methods could be due to the common assumption that most SLiMs occur outside globular domain regions. 198 of 452 SLiM that we reported are actually found on domain-domain interface; some of them are implicated in autoimmune and neurodegenerative diseases. We suggest that these SLiMs would be useful for designing inhibitors against the pathogenic protein complexes underlying these diseases. Our findings show that 3D structure-based SLiM detection algorithms can provide a more complete coverage of SLiM-mediated protein interactions than current sequence-based approaches. Contact: ksung@comp.nus.edu.sg. Supplementary information: Supplementary data are available at Bioinformatics online.

Original languageBritish English
Article numberbtq065
Pages (from-to)1036-1042
Number of pages7
JournalBioinformatics
Volume26
Issue number8
DOIs
StatePublished - 18 Feb 2010

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