Issue 1, 2012

Fuzziness: linking regulation to protein dynamics

Abstract

Proteins are dynamic creatures. Intrinsically disordered proteins (IDPs) function as multiplicity of structures and their activities can only be described by stochastic structure–function relationships. In their complex forms, however, IDPs were thought to lose their plasticity and behave similarly to globular proteins. Although various IDPs indeed fold upon binding, this view is not valid in general. IDPs usually interact with their partners via short motifs, which require malleable environments to function. Consequently, segments of IDPs could retain their disordered state in the complex, a phenomenon termed as fuzziness. Since its recognition, the number of structurally characterized fuzzy complexes, both with protein and DNA, rapidly increases. Here I review recent advances in our understanding of fuzziness. Four basic mechanisms are described how conformationally heterogeneous regions impact specificity or binding affinity of protein complexes. A novel allostery-model is proposed, where the regulatory site modulates the conformational equilibrium of the binding interface without adopting a unique structure. Proteinprotein interactions, post-translational modifications or alternative splicing of the highly flexible/disordered regions offer further opportunities for regulation and expand the functional repertoire of fuzzy complexes.

Graphical abstract: Fuzziness: linking regulation to protein dynamics

Article information

Article type
Review Article
Submitted
13 Jun 2011
Accepted
18 Aug 2011
First published
19 Sep 2011

Mol. BioSyst., 2012,8, 168-177

Fuzziness: linking regulation to protein dynamics

M. Fuxreiter, Mol. BioSyst., 2012, 8, 168 DOI: 10.1039/C1MB05234A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Spotlight

Advertisements