Jump to main content
Jump to site search

Issue 1, 2012
Previous Article Next Article

Attributes of short linear motifs

Author affiliations

Abstract

Traditionally, proteinprotein interactions were thought to be mediated by large, structured domains. However, it has become clear that the interactome comprises a wide range of binding interfaces with varying degrees of flexibility, ranging from rigid globular domains to disordered regions that natively lack structure. Enrichment for disorder in highly connected hub proteins and its correlation with organism complexity hint at the functional importance of disordered regions. Nevertheless, they have not yet been extensively characterised. Shifting the attention from globular domains to disordered regions of the proteome might bring us closer to elucidating the dense and complex connectivity of the interactome. An important class of disordered interfaces are the compact mono-partite, short linear motifs (SLiMs, or eukaryotic linear motifs (ELMs)). They are evolutionarily plastic and interact with relatively low affinity due to the limited number of residues that make direct contact with the binding partner. These features confer to SLiMs the ability to evolve convergently and mediate transient interactions, which is imperative to network evolution and to maintain robust cell signalling, respectively. The ability to discriminate biologically relevant SLiMs by means of different attributes will improve our understanding of the complexity of the interactome and aid development of bioinformatics tools for motif discovery. In this paper, the curated instances currently available in the Eukaryotic Linear Motif (ELM) database are analysed to provide a clear overview of the defining attributes of SLiMs. These analyses suggest that functional SLiMs have higher levels of conservation than their surrounding residues, frequently evolve convergently, preferentially occur in disordered regions and often form a secondary structure when bound to their interaction partner. These results advocate searching for small groupings of residues in disordered regions with higher relative conservation and a propensity to form the secondary structure. Finally, the most interesting conclusions are examined in regard to their functional consequences.

Graphical abstract: Attributes of short linear motifs

Back to tab navigation

Supplementary files

Publication details

The article was received on 09 Jun 2011, accepted on 08 Aug 2011 and first published on 12 Sep 2011


Article type: Paper
DOI: 10.1039/C1MB05231D
Citation: Mol. BioSyst., 2012,8, 268-281
  •   Request permissions

    Attributes of short linear motifs

    N. E. Davey, K. Van Roey, R. J. Weatheritt, G. Toedt, B. Uyar, B. Altenberg, A. Budd, F. Diella, H. Dinkel and T. J. Gibson, Mol. BioSyst., 2012, 8, 268
    DOI: 10.1039/C1MB05231D

Search articles by author

Spotlight

Advertisements