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Parkinson's disease

Disorder in the court

Nature volume 530, pages 38–39 (2016)Cite this article

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The native structure of the protein α-synuclein, which is implicated in Parkinson's disease, is controversial. In-cell nuclear magnetic resonance now shows that it remains disordered when loaded into living cells. See Article p.45

The 3D structure of a biological molecule typically dictates its function. In an apparent paradox, intrinsically disordered proteins (IDPs) lack well-defined 3D structures, but this structural plasticity can confer diverse biological functions. The small protein α-synuclein is an IDP in vitro, but whether it exists in vivo as a monomeric IDP1 or as an ordered, helical tetramer2,3 is a matter of dispute4. If α-synuclein is an ordered tetramer in vivo, it might be possible to design drugs that stabilize this protein state and prevent the protein from forming toxic aggregates, which are associated with Parkinson's disease. On page 45 of this issue, Theillet et al.5 describe a detailed analysis of the structure of α-synuclein inside living cells.

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Figure 1: Structure of a disordered protein in living cells.

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Authors and Affiliations

  1. T. Reid Alderson and Ad Bax are in the Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.,

    T. Reid Alderson & Ad Bax

  2. T.R.A. is also in the Department of Chemistry, University of Oxford, Oxford OX1 3TA, UK.,

    T. Reid Alderson

Authors
  1. T. Reid Alderson
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  2. Ad Bax
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Correspondence to T. Reid Alderson or Ad Bax.

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Parkinson's disease: Crystals of a toxic core

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Alderson, T., Bax, A. Disorder in the court. Nature 530, 38–39 (2016). https://doi.org/10.1038/nature16871

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