Intrinsic disorder in scaffold proteins: Getting more from less
302
TL;DR: It is concluded that ID can enhance scaffold function by a diverse array of mechanisms, and scaffold proteins utilize several ID-facilitated mechanisms to enhance function, and by doing so, get more functionality from less structure.
read more
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.
read more
Chat with Paper
AI Agents for this Paper
Find similar papers on Google Scholar, PubMed and Arxiv
Write a critical review of this paper
Analyze citations of this paper to find unaddressed research gaps
Citations
Classification of intrinsically disordered regions and proteins.
Robin van der Lee,Robin van der Lee,Marija Buljan,Benjamin Lang,Robert J. Weatheritt,Gary W. Daughdrill,A. Keith Dunker,Monika Fuxreiter,Julian Gough,Joerg Gsponer,David T. Jones,Philip M. Kim,Richard W. Kriwacki,Christopher J. Oldfield,Rohit V. Pappu,Peter Tompa,Peter Tompa,Vladimir N. Uversky,Vladimir N. Uversky,Peter E. Wright,M. Madan Babu +20 more
TL;DR: Characterization of unannotated and uncharacterized protein segments is expected to lead to the discovery of novel functions as well as provide important insights into existing biological processes and is likely to shed new light on molecular mechanisms of diseases that are not yet fully understood.
Understanding protein non-folding.
TL;DR: This review describes the family of intrinsically disordered proteins, members of which fail to form rigid 3-D structures under physiological conditions, either along their entire lengths or only in localized regions.
1.5K
Intrinsically disordered proteins and intrinsically disordered protein regions.
TL;DR: This work presents several early examples and the mechanisms by which IDPs contribute to function, which it hopes will encourage comprehensive discussion of IDPs and IDP regions in biochemistry textbooks and propose future directions for IDP research.
1K
Classification of Intrinsically Disordered Regions and Proteins
Robin van der Lee,Robin van der Lee,Marija Buljan,Benjamin Lang,Robert J. Weatheritt,Gary W. Daughdrill,A. Keith Dunker,Monika Fuxreiter,Julian Gough,Joerg Gsponer,David T. Jones,Philip M. Kim,Richard W. Kriwacki,Christopher J. Oldfield,Rohit V. Pappu,Peter Tompa,Peter Tompa,Vladimir N. Uversky,Vladimir N. Uversky,Peter E. Wright,M. Madan Babu +20 more
- 09 Jul 2014
TL;DR: Uncharacterized and uncharacterized protein segments are likely to be a large source of functional novelty relevant for discovering new biology as discussed by the authors, which is likely to lead to the discovery of novel functions as well as provide important insights into existing biological processes.
969
Introducing Protein Intrinsic Disorder.
Johnny Habchi,Peter Tompa,Peter Tompa,Sonia Longhi,Sonia Longhi,Vladimir N. Uversky,Vladimir N. Uversky +6 more
TL;DR: This paper presents a meta-anatomy of the determinants of Macromolećules Biologiques, a probabilistic framework for estimating the number of components in a Response to Enzymology.
References
Mechanism of coupled folding and binding of an intrinsically disordered protein
TL;DR: Using NMR titrations and 15N relaxation dispersion, it is shown that the phosphorylated kinase inducible activation domain (pKID) of the transcription factor CREB forms an ensemble of transient encounter complexes on binding to the KIX domain of the CREB binding protein.
The pairwise energy content estimated from amino acid composition discriminates between folded and intrinsically unstructured proteins.
TL;DR: IUPred, a novel method for estimating the total pairwise interaction energy of proteins of known structure, based on a quadratic form in the amino acid composition of the protein, is presented and substantiates the concept of protein disorder.
1K
Clustering of Shaker-type K + channels by interaction with a family of membrane-associated guanylate kinases
TL;DR: Functional and biochemical evidence is presented that cell-surface clustering of Shaker-subfamily K+ channels is mediated by the PSD-95 family of membrane-associated putative guanylate kinases, and the ability of PDZ domains to function as independent modules for protein–protein interaction, and their presence in other junction-associated molecules suggest that PDZ-domain-containing polypeptides may be widely involved in the organization of proteins at sites of membrane specialization.
1K
GlobPlot: exploring protein sequences for globularity and disorder
TL;DR: A new tool for discovery of unstructured, or disordered regions within proteins, and examples with known proteins where it successfully identifies inter-domain segments containing linear motifs, and also apparently ordered regions that do not contain any recognised domain are presented.
MAP Kinase Pathways in the Yeast Saccharomyces cerevisiae
TL;DR: The current knowledge of MAPK pathways in yeast is presented and some directions for future research in this area are presented, including how the upstream proteins actually activate the cascade remains unclear.
1K