Conditionally disordered proteins: bringing the environment back into the fold

Andrew Hausrath, Richard L. Kingston

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

For many proteins, biological function requires the folding of the polypeptide chain into a unique and persistent tertiary structure. This review concerns proteins that adopt a specific tertiary structure to function, but are otherwise partially or completely disordered. The biological cue for protein folding is environmental perturbation or minor post-translational modification. Hence, we term these proteins conditionally disordered. Many of these proteins recognize and bind other molecules, and conditional disorder has been hypothesized to allow for more nuanced control and regulation of binding processes. However, this remains largely unproven. The sequences of conditionally disordered proteins suggest their propensity to fold; yet, under the standard laboratory conditions, they do not do so, which may appear surprising. We argue that the surprise results from the failure to consider the role of the environment in protein structure formation and that conditional disorder arises as a natural consequence of the marginal stability of the folded state.

Original languageEnglish (US)
Pages (from-to)1-14
Number of pages14
JournalCellular and Molecular Life Sciences
DOIs
StateAccepted/In press - Jun 8 2017
Externally publishedYes

Fingerprint

Proteins
Protein Folding
Post Translational Protein Processing
Cues
Peptides

Keywords

  • Conformational fluctuations
  • Coupled binding and folding
  • Osmolytes
  • Protein stability
  • Unstable proteins

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Conditionally disordered proteins : bringing the environment back into the fold. / Hausrath, Andrew; Kingston, Richard L.

In: Cellular and Molecular Life Sciences, 08.06.2017, p. 1-14.

Research output: Contribution to journalArticle

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