Deckert, Annika and Waudby, Christopher and Wlodarski, Tomasz and Wentink, Anne and Wang, Xiaolin and Kirkpatrick, John and Paton, Jack and Camilloni, C. and Kukic, P. and Dobson, C.M. and Vendruscolo, M. and Cabrita, Lisa and Christodoulou, John (2016) Structural characterization of the interaction of α-synuclein nascent chains with the ribosomal surface and trigger factor. Proceedings of the National Academy of Sciences of the United States of America 113 (18), pp. 5012-5017. ISSN 0027-8424.
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Abstract
The ribosome is increasingly becoming recognized as a key hub for integrating quality control processes associated with protein biosynthesis and cotranslational folding (CTF). The molecular mechanisms by which these processes take place, however, remain largely unknown, in particular in the case of intrinsically disordered proteins (IDPs). To address this question, we studied at a residue-specific level the structure and dynamics of ribosome-nascent chain complexes (RNCs) of α-synuclein (αSyn), an IDP associated with Parkinson’s disease (PD). Using solution-state nuclear magnetic resonance (NMR) spectroscopy and coarse-grained molecular dynamics (MD) simulations, we find that, although the nascent chain (NC) has a highly disordered conformation, its N-terminal region shows resonance broadening consistent with interactions involving specific regions of the ribosome surface. We also investigated the effects of the ribosome-associated molecular chaperone trigger factor (TF) on αSyn structure and dynamics using resonance broadening to define a footprint of the TF–RNC interactions. We have used these data to construct structural models that suggest specific ways by which emerging NCs can interact with the biosynthesis and quality control machinery.
Metadata
| Item Type: | Article |
|---|---|
| Keyword(s) / Subject(s): | NMR spectroscopy, ribosome, nascent chain, α-synuclein, cotranslational folding |
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Research Centres and Institutes: | Structural Molecular Biology, Institute of (ISMB) |
| Depositing User: | Administrator |
| Date Deposited: | 13 May 2016 09:52 |
| Last Modified: | 02 Aug 2023 17:23 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/15165 |
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