Intrinsically disordered proteins: An update

A. Keith Dunker, Christopher J. Oldfield, Jingwei Meng, Pedro Romero, Jack Y. Yang, Zoran Obradovic, Vladimir N. Uversky

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Scopus citations

Abstract

Just over 10 years ago, in June, 1997, in the Proceedings of the IEEE International Conference on Neural Networks, we published our first predictor of intrinsically disordered protein [1]. Since then, we have substantially improved our predictors, and more than 20 other laboratory groups have joined in efforts to improve the prediction of protein disorder. At the algorithmic level, prediction of protein intrinsic disorder is similar to the prediction of secondary structure, but, at the structural level, secondary structure and intrinsic disorder are entirely different. The secondary structure class called random coil or irregular differs from intrinsic disorder due to very different dynamic properties, with the secondary structure class being much less mobile than the region of disorder. At the biological level, unlike the prediction of secondary structure, the prediction of intrinsic disorder has been revolutionary. That is, for many years, experimentalists have provided evidence that some proteins lack fixed structure or are disordered (or unfolded) under physiological conditions. Experimentalists further are showing that, for some proteins, functions depended on the unstructured rather than structured state. However, these examples have been mostly ignored. To our knowledge, not one disordered protein or disorder-associated function is discussed in any biochemistry textbook, even though such examples began to be discovered more than 50 years ago. Disorder prediction has been important for showing that the few experimentally characterized examples represent a very large cohort that is found all across all three domains of life. We now know that many significant biological functions depend directly on, or are importantly associated with, the unfolded or partially folded state. In this paper, we will briefly review some of the key discoveries that have occurred in the last decade, and, furthermore, will make a few highly speculative projections.

Original languageEnglish (US)
Title of host publicationProceedings of the 7th IEEE International Conference on Bioinformatics and Bioengineering, BIBE
Pages49-58
Number of pages10
DOIs
StatePublished - Dec 1 2007
Event7th IEEE International Conference on Bioinformatics and Bioengineering, BIBE - Boston, MA, United States
Duration: Jan 14 2007Jan 17 2007

Publication series

NameProceedings of the 7th IEEE International Conference on Bioinformatics and Bioengineering, BIBE

Other

Other7th IEEE International Conference on Bioinformatics and Bioengineering, BIBE
CountryUnited States
CityBoston, MA
Period1/14/071/17/07

Keywords

  • Alternative splicing
  • And disorder-based drug discovery
  • Cell signaling
  • Disorder prediction
  • Protein-protein interactions
  • Regulation and control

ASJC Scopus subject areas

  • Biotechnology
  • Genetics
  • Bioengineering

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