Natively disordered proteins: Functions and predictions

Pedro Romero, Zoran Obradovic, A. Keith Dunker

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Proteins can exist in at least three forms: the ordered form (solid-like), the partially folded form (collapsed, molten globule-like or liquid-like) and the extended form (extended, random coil-like or gas-like). The protein trinity hypothesis has two components: (i) a given native protein can be in any one of the three forms, depending on the sequence and the environment; and (ii) function can arise from any one of the three forms or from transitions between them. In this study, bioinformatics and data mining were used to investigate intrinsic disorder in proteins and develop neural network-based predictors of natural disordered regions (PONDR) that can discriminate between ordered and disordered residues with up to 84% accuracy. Predictions of intrinsic disorder indicate that the three kingdoms follow the disorder ranking eubacteria < archaebacteria ≪ eukaryotes, with approximately half of eukaryotic proteins predicted to contain substantial regions of intrinsic disorder. Many of the known disordered regions are involved in signalling, regulation or control. Involvement of highly flexible or disordered regions in signalling is logical: a flexible sensor more readily undergoes conformational change in response to environmental perturbations than does a rigid one. Thus, the increased disorder in the eukaryotes is likely the direct result of an increased need for signalling and regulation in nucleated organisms. PONDR can also be used to detect molecular recognition elements that are disordered in the unbound state and become structured when bound to a biologically meaningful partner. Application of disorder predictions to cell-signalling, cancer-associated and control protein databases supports the widespread occurrence of protein disorder in these processes.

Original languageEnglish (US)
Pages (from-to)105-113
Number of pages9
JournalApplied Bioinformatics
Volume3
Issue number2-3
DOIs
StatePublished - Dec 1 2004

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Proteins
prediction
proteins
Eukaryota
eukaryotic cells
Protein Databases
Data Mining
Cell signaling
Archaea
Eubacteria
Molecular recognition
Computational Biology
Bioinformatics
bioinformatics
neural networks
Gases
Data mining
Molten materials
Bacteria
gases

ASJC Scopus subject areas

  • Information Systems
  • Agricultural and Biological Sciences(all)
  • Computer Science Applications

Cite this

Natively disordered proteins : Functions and predictions. / Romero, Pedro; Obradovic, Zoran; Dunker, A. Keith.

In: Applied Bioinformatics, Vol. 3, No. 2-3, 01.12.2004, p. 105-113.

Research output: Contribution to journalArticle

Romero, Pedro ; Obradovic, Zoran ; Dunker, A. Keith. / Natively disordered proteins : Functions and predictions. In: Applied Bioinformatics. 2004 ; Vol. 3, No. 2-3. pp. 105-113.
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