title: Experimental detection of short regulatory motifs in eukaryotic proteins: tips for good practice as well as for bad.
abstract: It has become clear in outline though not yet in detail how cellular regulatory and signalling systems are constructed. The essential machines are protein complexes that effect regulatory decisions by undergoing internal changes of state. Subcomponents of these cellular complexes are assembled into molecular switches. Many of these switches employ one or more short peptide motifs as toggles that can move between one or more sites within the switch system, the simplest being on-off switches. Paradoxically, these motif modules (termed short linear motifs or SLiMs) are both hugely abundant but difficult to research. So despite the many successes in identifying short regulatory protein motifs, it is thought that only the "tip of the iceberg" has been exposed. Experimental and bioinformatic motif discovery remain challenging and error prone. The advice presented in this article is aimed at helping researchers to uncover genuine protein motifs, whilst avoiding the pitfalls that lead to reports of false discovery.
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, D69117, Heidelberg, Germany. toby.gibson@embl.de.
authors.forename: Toby J
authors.initials: TJ
authors.lastname: Gibson
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, D69117, Heidelberg, Germany. dinkel@embl.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Dinkel
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, D69117, Heidelberg, Germany. roey@embl.de.|Health Services Research Unit, Operational Direction Public Health and Surveillance, Scientific Institute of Public Health (WIV-ISP), 1050, Brussels, Belgium. roey@embl.de.
authors.forename: Kim
authors.initials: K
authors.lastname: Van Roey
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, D69117, Heidelberg, Germany. diella@embl.de.
authors.forename: Francesca
authors.initials: F
authors.lastname: Diella
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D019295:Computational Biology; D056890:Eukaryota / Q000378:metabolism*; D005820:Genetic Testing; D006801:Humans; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D011506:Proteins