Intrinsic disorder in scaffold proteins

Getting more from less

Marc S. Cortese, Vladimir N. Uversky, A. Dunker

Research output: Contribution to journalArticle

173 Citations (Scopus)

Abstract

Regulation, recognition and cell signaling involve the coordinated actions of many players. Signaling scaffolds, with their ability to bring together proteins belonging to common and/or interlinked pathways, play crucial roles in orchestrating numerous events by coordinating specific interactions among signaling proteins. This review examines the roles of intrinsic disorder (ID) in signaling scaffold protein function. Several well-characterized scaffold proteins with structurally and functionally characterized ID regions are used here to illustrate the importance of ID for scaffolding function. These examples include scaffolds that are mostly disordered, only partially disordered or those in which the ID resides in a scaffold partner. Specific scaffolds discussed include RNase, voltage-activated potassium channels, axin, BRCA1, GSK-3β, p53, Ste5, titin, Fus3, BRCA1, MAP2, D-AKAP2 and AKAP250. Among the mechanisms discussed are: molecular recognition features, fly-casting, ease of encounter complex formation, structural isolation of partners, modulation of interactions between bound partners, masking of intramolecular interaction sites, maximized interaction surface per residue, toleration of high evolutionary rates, binding site overlap, allosteric modification, palindromic binding, reduced constraints for alternative splicing, efficient regulation via posttranslational modification, efficient regulation via rapid degradation, protection of normally solvent-exposed sites, enhancing the plasticity of interaction and molecular crowding. We conclude that ID can enhance scaffold function by a diverse array of mechanisms. In other words, scaffold proteins utilize several ID-facilitated mechanisms to enhance function, and by doing so, get more functionality from less structure.

Original languageEnglish
Pages (from-to)85-106
Number of pages22
JournalProgress in Biophysics and Molecular Biology
Volume98
Issue number1
DOIs
StatePublished - Sep 2008

Fingerprint

Proteins
Connectin
Glycogen Synthase Kinase 3
Crowding
Aptitude
Potassium Channels
Alternative Splicing
Post Translational Protein Processing
Ribonucleases
Diptera
Binding Sites

Keywords

  • Intrinsic disorder
  • Scaffold
  • Signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics

Cite this

Intrinsic disorder in scaffold proteins : Getting more from less. / Cortese, Marc S.; Uversky, Vladimir N.; Dunker, A.

In: Progress in Biophysics and Molecular Biology, Vol. 98, No. 1, 09.2008, p. 85-106.

Research output: Contribution to journalArticle

Cortese, Marc S. ; Uversky, Vladimir N. ; Dunker, A. / Intrinsic disorder in scaffold proteins : Getting more from less. In: Progress in Biophysics and Molecular Biology. 2008 ; Vol. 98, No. 1. pp. 85-106.
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