High levels of structural disorder in scaffold proteins as exemplified by a novel neuronal protein, CASK-interactive protein1

Annamária Balázs, Veronika Csizmok, L. Buday, Marianna Rakács, Robert Kiss, M. Bokor, Roopesh Udupa, K. Tompa, Peter Tompa

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

CASK-interactive protein1 is a newly recognized post-synaptic density protein in mammalian neurons. Although its N-terminal region contains several well-known functional domains, its entire C-terminal proline-rich region of 800 amino acids lacks detectable sequence homology to any previously characterized protein. We used multiple techniques for the structural characterization of this region and its three fragments. By bioinformatics predictions, CD spectroscopy, wide-line and 1H-NMR spectroscopy, limited proteolysis and gel filtration chromatography, we provided evidence that the entire proline-rich region of CASK-interactive protein1 is intrinsically disordered. We also showed that the proline-rich region is biochemically functional, as it interacts with the adaptor protein Abl-interactor-2. To extend the finding of a high level of disorder in this scaffold protein, we collected 74 scaffold proteins (also including proteins denoted as anchor and docking), and predicted their disorder by three different algorithms. We found that a very high fraction (53.6% on average) of the residues fall into local disorder and their ordered domains are connected by linker regions which are mostly disordered (64.5% on average). Because of this high frequency of disorder, the usual design of scaffold proteins of short globular domains (86 amino acids on average) connected by longer linker regions (140 amino acids on average) and the noted binding functions of these regions in both CASK-interactive protein1 and the other proteins studied, we suggest that structurally disordered regions prevail and play key recognition roles in scaffold proteins.

Original languageEnglish
Pages (from-to)4168-4180
Number of pages13
JournalFEBS Journal
Volume276
Issue number14
DOIs
Publication statusPublished - Jul 2009

Fingerprint

Scaffolds
Proteins
Proline
Amino Acids
Proteolysis
Post-Synaptic Density
Bioinformatics
Sequence Homology
Chromatography
Computational Biology
Anchors
Nuclear magnetic resonance spectroscopy
Neurons
Gel Chromatography
Spectrum Analysis
Magnetic Resonance Spectroscopy
Gels
Spectroscopy

Keywords

  • Anchor
  • Docking
  • Post-synaptic density
  • Scaffold
  • Unstructured

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

High levels of structural disorder in scaffold proteins as exemplified by a novel neuronal protein, CASK-interactive protein1. / Balázs, Annamária; Csizmok, Veronika; Buday, L.; Rakács, Marianna; Kiss, Robert; Bokor, M.; Udupa, Roopesh; Tompa, K.; Tompa, Peter.

In: FEBS Journal, Vol. 276, No. 14, 07.2009, p. 4168-4180.

Research output: Contribution to journalArticle

Balázs, Annamária ; Csizmok, Veronika ; Buday, L. ; Rakács, Marianna ; Kiss, Robert ; Bokor, M. ; Udupa, Roopesh ; Tompa, K. ; Tompa, Peter. / High levels of structural disorder in scaffold proteins as exemplified by a novel neuronal protein, CASK-interactive protein1. In: FEBS Journal. 2009 ; Vol. 276, No. 14. pp. 4168-4180.
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