ORCID Profile
0000-0003-1468-5138
Current Organisations
Institute of Biochemistry and Biophysics, Polish Academy of Sciences
,
University of Oxford
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Publisher: Massachusetts Medical Society
Date: 08-09-2016
Publisher: Proceedings of the National Academy of Sciences
Date: 10-09-2018
Abstract: Efficient synthesis and folding of proteins, avoiding misfolded states, are central to cell function. As folding may be initiated in parallel with translation, key experimental challenges are to map changes that occur in folding free energy landscapes as translation proceeds and to understand how these landscapes might be modulated by the ribosome and auxiliary factors. Here, we study the length-dependent folding of a domain from a tandem repeat protein and solve the structure of a stable folding intermediate. Although destabilized by the ribosome at equilibrium, modeling of the nonequilibrium folding pathway nevertheless indicates a significant role for proline isomerization during translation. We develop a simple model to explore the impact of cotranslational folding kinetics on misfolding hazards.
Publisher: Springer Science and Business Media LLC
Date: 14-10-2021
DOI: 10.1038/S41557-021-00796-X
Abstract: Most proteins begin to fold during biosynthesis on the ribosome. It has been suggested that interactions between the emerging polypeptide and the ribosome surface might allow the ribosome itself to modulate co-translational folding. Here we combine protein engineering and NMR spectroscopy to characterize a series of interactions between the ribosome surface and unfolded nascent chains of the immunoglobulin-like FLN5 filamin domain. The strongest interactions are found for a C-terminal segment that is essential for folding, and we demonstrate quantitative agreement between the strength of this interaction and the energetics of the co-translational folding process itself. Mutations in this region that reduce the extent of binding result in a shift in the co-translational folding equilibrium towards the native state. Our results therefore demonstrate that a competition between folding and binding provides a simple, dynamic mechanism for the modulation of co-translational folding by the ribosome.
Publisher: Springer Science and Business Media LLC
Date: 29-02-2016
DOI: 10.1038/NSMB.3182
Publisher: Proceedings of the National Academy of Sciences
Date: 18-04-2016
Abstract: Protein biosynthesis is carried out by ribosomes, the macromolecular machines present in all kingdoms of life. Aided by molecular chaperones, nascent proteins can begin to fold while emerging from the ribosome. Achieving their native fold, and avoiding misfolding, is thereby crucial for the fate of all newly synthesized proteins. The molecular details of this fundamental process, however, are poorly understood. In this work we develop a combined NMR and molecular simulation approach to characterize the behavior during biosynthesis of α-synuclein (αSyn), an intrinsically disordered protein associated with Parkinson’s disease. The detailed interactions of αSyn with the ribosome surface and with trigger factor, a ribosome-associated chaperone, reveal the first steps of how a nascent chain emerges from the ribosome.
Publisher: Springer Science and Business Media LLC
Date: 16-09-2022
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1SC04313G
Abstract: NMR measurements of methyl relaxation in translationally-arrested ribosome–nascent chain complexes probe the dynamics of folded nascent polypeptides emerging during biosynthesis and quantify their interaction with the ribosome surface.
Location: Poland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: Thailand
No related grants have been discovered for Weerawat Phuklia.