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To be disordered or not to be disordered: is that still a question for proteins in the cell?

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Abstract

There is ample evidence that many proteins or regions of proteins lack a well-defined folded structure under native-like conditions. These are called intrinsically disordered proteins (IDPs) or intrinsically disordered regions (IDRs). Whether this intrinsic disorder is also their main structural characteristic in living cells has been a matter of intense debate. The structural analysis of IDPs became an important challenge also because of their involvement in a plethora of human diseases, which made IDPs attractive targets for therapeutic development. Therefore, biophysical approaches are increasingly being employed to probe the structural and dynamical state of proteins, not only in isolation in a test tube, but also in a complex biological environment and even within intact cells. Here, we survey direct and indirect evidence that structural disorder is in fact the physiological state of many proteins in the proteome. The paradigmatic case of α-synuclein is used to illustrate the controversial nature of this topic.

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Fig. 1
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Adapted from Ref. [151]

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Reprinted from Ref. [119]. Copyright 2012 American Society for Biochemistry and Molecular Biology

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Acknowledgements

This work was supported by the Odysseus Grant G.0029.12 from Research Foundation Flanders (FWO). KP is the recipient of a FWO long-term postdoctoral fellowship. The authors thank Jesper Oemig, Katrien Willegems and Alexander Shkumatov for useful discussions.

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  1. Kris Pauwels and Pierre Lebrun contributed equally.

Authors and Affiliations

  1. VIB-VUB Center for Structural Biology (CSB), Vlaams Instituut voor Biotechnologie (VIB), Brussels, Belgium

    Kris Pauwels, Pierre Lebrun & Peter Tompa

  2. Structural Biology Brussels (SBB), Vrije Universiteit Brussel (VUB), Brussels, Belgium

    Kris Pauwels, Pierre Lebrun & Peter Tompa

  3. Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, Hungary

    Peter Tompa

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  1. Kris Pauwels
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  2. Pierre Lebrun
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Pauwels, K., Lebrun, P. & Tompa, P. To be disordered or not to be disordered: is that still a question for proteins in the cell?. Cell. Mol. Life Sci. 74, 3185–3204 (2017). https://doi.org/10.1007/s00018-017-2561-6

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