Close encounters of the third kind: Disordered domains and the interactions of proteins

Peter Tompa, M. Fuxreiter, Christopher J. Oldfield, I. Simon, A. Keith Dunker, Vladimir N. Uversky

Research output: Contribution to journalArticle

177 Citations (Scopus)

Abstract

Protein-protein interactions are thought to be mediated by domains, which are autonomous folding units of proteins. Recently, a second type of interaction has been suggested, mediated by short segments termed linear motifs, which are related to recognition elements of intrinsically disordered regions. Here, we propose a third kind of protein-protein recognition mechanism, mediated by disordered regions longer than 20-30 residues. Bioinformatics predictions and well-characterized examples, such as the kinase-inhibitory domain of Cdk inhibitors and the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 of actin-binding proteins, show that these disordered regions conform to the definition of domains rather than motifs, i.e., they represent functional, evolutionary, and structural units. Their functions are distinct from those of short motifs and ordered domains, and establish a third kind of interaction principle. With these points, we argue that these long disordered regions should be recognized as a distinct class of biologically functional protein domains.

Original languageEnglish
Pages (from-to)328-335
Number of pages8
JournalBioEssays
Volume31
Issue number3
DOIs
Publication statusPublished - 2009

Fingerprint

Protein Interaction Domains and Motifs
Proteins
Wiskott-Aldrich Syndrome Protein
Microfilament Proteins
Protein Folding
Computational Biology
Phosphotransferases
Bioinformatics
Protein Domains

Keywords

  • Disorder in pfam
  • Disordered domain
  • Intrinsically disordered
  • Intrinsically unstructured
  • Pfam domain
  • Unstructured domain

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Close encounters of the third kind : Disordered domains and the interactions of proteins. / Tompa, Peter; Fuxreiter, M.; Oldfield, Christopher J.; Simon, I.; Dunker, A. Keith; Uversky, Vladimir N.

In: BioEssays, Vol. 31, No. 3, 2009, p. 328-335.

Research output: Contribution to journalArticle

Tompa, Peter ; Fuxreiter, M. ; Oldfield, Christopher J. ; Simon, I. ; Dunker, A. Keith ; Uversky, Vladimir N. / Close encounters of the third kind : Disordered domains and the interactions of proteins. In: BioEssays. 2009 ; Vol. 31, No. 3. pp. 328-335.
@article{f4bd54b32e3f4ffbaae33acc2019ffcb,
title = "Close encounters of the third kind: Disordered domains and the interactions of proteins",
abstract = "Protein-protein interactions are thought to be mediated by domains, which are autonomous folding units of proteins. Recently, a second type of interaction has been suggested, mediated by short segments termed linear motifs, which are related to recognition elements of intrinsically disordered regions. Here, we propose a third kind of protein-protein recognition mechanism, mediated by disordered regions longer than 20-30 residues. Bioinformatics predictions and well-characterized examples, such as the kinase-inhibitory domain of Cdk inhibitors and the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 of actin-binding proteins, show that these disordered regions conform to the definition of domains rather than motifs, i.e., they represent functional, evolutionary, and structural units. Their functions are distinct from those of short motifs and ordered domains, and establish a third kind of interaction principle. With these points, we argue that these long disordered regions should be recognized as a distinct class of biologically functional protein domains.",
keywords = "Disorder in pfam, Disordered domain, Intrinsically disordered, Intrinsically unstructured, Pfam domain, Unstructured domain",
author = "Peter Tompa and M. Fuxreiter and Oldfield, {Christopher J.} and I. Simon and Dunker, {A. Keith} and Uversky, {Vladimir N.}",
year = "2009",
doi = "10.1002/bies.200800151",
language = "English",
volume = "31",
pages = "328--335",
journal = "BioEssays",
issn = "0265-9247",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

TY - JOUR

T1 - Close encounters of the third kind

T2 - Disordered domains and the interactions of proteins

AU - Tompa, Peter

AU - Fuxreiter, M.

AU - Oldfield, Christopher J.

AU - Simon, I.

AU - Dunker, A. Keith

AU - Uversky, Vladimir N.

PY - 2009

Y1 - 2009

N2 - Protein-protein interactions are thought to be mediated by domains, which are autonomous folding units of proteins. Recently, a second type of interaction has been suggested, mediated by short segments termed linear motifs, which are related to recognition elements of intrinsically disordered regions. Here, we propose a third kind of protein-protein recognition mechanism, mediated by disordered regions longer than 20-30 residues. Bioinformatics predictions and well-characterized examples, such as the kinase-inhibitory domain of Cdk inhibitors and the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 of actin-binding proteins, show that these disordered regions conform to the definition of domains rather than motifs, i.e., they represent functional, evolutionary, and structural units. Their functions are distinct from those of short motifs and ordered domains, and establish a third kind of interaction principle. With these points, we argue that these long disordered regions should be recognized as a distinct class of biologically functional protein domains.

AB - Protein-protein interactions are thought to be mediated by domains, which are autonomous folding units of proteins. Recently, a second type of interaction has been suggested, mediated by short segments termed linear motifs, which are related to recognition elements of intrinsically disordered regions. Here, we propose a third kind of protein-protein recognition mechanism, mediated by disordered regions longer than 20-30 residues. Bioinformatics predictions and well-characterized examples, such as the kinase-inhibitory domain of Cdk inhibitors and the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 of actin-binding proteins, show that these disordered regions conform to the definition of domains rather than motifs, i.e., they represent functional, evolutionary, and structural units. Their functions are distinct from those of short motifs and ordered domains, and establish a third kind of interaction principle. With these points, we argue that these long disordered regions should be recognized as a distinct class of biologically functional protein domains.

KW - Disorder in pfam

KW - Disordered domain

KW - Intrinsically disordered

KW - Intrinsically unstructured

KW - Pfam domain

KW - Unstructured domain

UR - http://www.scopus.com/inward/record.url?scp=65249102824&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65249102824&partnerID=8YFLogxK

U2 - 10.1002/bies.200800151

DO - 10.1002/bies.200800151

M3 - Article

C2 - 19260013

AN - SCOPUS:65249102824

VL - 31

SP - 328

EP - 335

JO - BioEssays

JF - BioEssays

SN - 0265-9247

IS - 3

ER -