ELM: the status of the 2010 eukaryotic linear motif resource

Abstract

Linear motifs are short segments of multidomain proteins that provide regulatory functions independently of protein tertiary structure. Much of intracellular signalling passes through protein modifications at linear motifs. Many thousands of linear motif instances, most notably phosphorylation sites, have now been reported. Although clearly very abundant, linear motifs are difficult to predict de novo in protein sequences due to the difficulty of obtaining robust statistical assessments. The ELM resource at http://elm.eu.org/ provides an expanding knowledge base, currently covering 146 known motifs, with annotation that includes >1300 experimentally reported instances. ELM is also an exploratory tool for suggesting new candidates of known linear motifs in proteins of interest. Information about protein domains, protein structure and native disorder, cellular and taxonomic contexts is used to reduce or deprecate false positive matches. Results are graphically displayed in a ‘Bar Code’ format, which also displays known instances from homologous proteins through a novel ‘Instance Mapper’ protocol based on PHI-BLAST. ELM server output provides links to the ELM annotation as well as to a number of remote resources. Using the links, researchers can explore the motifs, proteins, complex structures and associated literature to evaluate whether candidate motifs might be worth experimental investigation.

Fly cryptochrome and the visual system

“…The computational search for dCRY protein-protein interactions combined the results from the STRING database (19) of proteinprotein interactions with the domain organization of proteins from Pfam (48). Relevant proteins were analyzed with CSpritz (26), which predicts intrinsic disorder in the sequence as well as linear motifs coding for common protein-peptide interactions taken from ELM (49). The X-ray structures of INAD PDZ domains were retrieved from the Protein Data Bank for domains 1 and 5 [Protein Data Bank (PDB) codes 1IHJ and 2QKT].…”

Cyclin B1 interacts with the BH3-only protein Bim and mediates its phosphorylation by Cdk1 during mitosis

“…Members of the cyclin family can recognize substrates through either Cy or RxL motifs (where X is any amino acid), allowing substrate phosphorylation by their Cdk binding partner. 37 Using the in silico program, eukaryotic linear motif (ELM), 38 two cyclin binding sites were detected at the C and N termini of BimEL and BimL, which suggests that Bim can directly bind to cyclin B1 during mitosis. To examine this further, K562 cells were treated with either vehicle [DMSO (0.1% v/v)] or Nocodazole (1 μM) for 16 h, and Bim was immunoprecipitated from cell extracts.…”

Exploring the binding diversity of intrinsically disordered proteins involved in one‐to‐many binding

“…With regard to IDP regions involved in binding, various descriptors have been used, such as eukaryotic linear motif (ELMs), 34,35 linear motifs (LMs), 36 short linear motif (SLiMs), 37,38 regions of increased structural propensity (RISPs), 39 and molecular recognition features (MoRFs). 40 All of these describe similar phenomena, despite differing approaches used by the various researchers for identification of binding segments.…”

“…41,42 Predicting binding sites by sequence matches to the motifs of ELMs, 34,35 LMs, 36 SLiMs, 37,38 or other collections of sequence patterns [43][44][45] provides one strategy for identifying potential binding sites located within IDPs or IDP regions. Using sequence characteristics that indicate short binding regions within longer regions of disorder offers a second strategy that does not depend on specific motifs, and several predictors have been developed that use this second strategy.…”