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The Institute of Physics Colloquium

Konwersatorium Online

Kinetic control of protein folding: Topological traps and a new class of misfolding

27-02-2024 15:15 - 16:15
Zoom - Institute of Physics PAS, Warsaw
Professor Edward Patrick O'Brien
Pennsylvania State University, University Park, USA

I will present computational and experimental evidence suggesting there exists a previously unrecognized, widespread class of monomeric protein misfolding that can explain decades-old biochemical and molecular biology data, such as how synonymous mutations can alter protein function over long time scales in vivo [Nat. Chem. 2023], the origin of stretched exponential protein folding kinetics, and how some soluble misfolded proteins can bypass the refolding action of chaperones [Nat. Comm. 2023]. This new class of misfolding involves the formation or loss of non-covalent lasso entanglements, which are composed of a backbone loop topologically closed by a non-covalent interaction between residues and the threading of that loop by either an N- or C-terminal backbone segment. Indeed, a retrospective analysis of previously published all-atom protein folding simulations finds the presence of these misfolded states [Biorxiv. 2022]. Thus, the formation of these non-native entangled motifs are opening up new perspectives and offering new explanations to old questions.


List of Dates (Page event details)

  • 27-02-2024 15:15 - 16:15
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