Structural characterization of the interaction of α-synuclein nascent chains with the ribosomal surface and trigger factor
Articolo
Data di Pubblicazione:
2016
Citazione:
Structural characterization of the interaction of α-synuclein nascent chains with the ribosomal surface and trigger factor / A. Deckert, C.A. Waudby, T. Wlodarski, A.S. Wentink, X. Wang, J.P. Kirkpatrick, J.F.S. Paton, C. Camilloni, P. Kukic, C.M. Dobson, M. Vendruscolo, L.D. Cabrita, J. Christodoulou. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 113:18(2016 May), pp. 5012-5017. [10.1073/pnas.1519124113]
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 highlydisordered 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 ribosomeassociated 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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
cotranslational folding; nascent chain; NMR spectroscopy; ribosome; α-synuclein;binding sites; computer simulation; protein binding; protein conformation; protein domains; ribosomes; surface properties; alpha-synuclein; models, chemical; molecular docking simulation; multidisciplinary
Elenco autori:
A. Deckert, C.A. Waudby, T. Wlodarski, A.S. Wentink, X. Wang, J.P. Kirkpatrick, J.F.S. Paton, C. Camilloni, P. Kukic, C.M. Dobson, M. Vendruscolo, L.D. Cabrita, J. Christodoulou
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