Regensburg 2016 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 24: Posters - Single Molecule Biophysics
BP 24.1: Poster
Montag, 7. März 2016, 17:30–19:30, Poster C
Knotting and Unknotting of a single protein with optical tweezers — •Fabian Ziegler1, Nicole Lim1, Soumit Mandal2, Benjamin Pelz1, Wei-Ping Ng2, Sophie Jackson2, and Matthias Rief1 — 1Physik-Department E22, TU München (Germany) — 2University of Cambridge (UK)
Spontaneous folding of a polypeptide chain into a knotted structure remains one of the most puzzling and fascinating features of protein folding. However the observed kinetics are on the timescale of minutes and thus hard to reproduce with atomistic simulations yet.
Former studies could not distinguish between folding and knotting steps in the formation of the knotted native structure, as it has generally not been possible to control the topology of the unfolded state. We have overcome this problem with Single-molecule Force Spectroscopy by variation of pulling directions and can provide direct evidence that a threading event associated with knot formation significantly slows down folding of native UCH-L1, an important enzyme in the proteosomal degradation that has mutations linked to Parkinson's disease and has been identified as a target for treatment of Alzheimer's disease.
Our results highlight the complex nature of the folding of a knotted protein, and detect many additional intermediate structures. Mechanical stretching of knotted proteins is also important for understanding the possible implications of knots in proteins for cellular degradation. Our results might therefore indicate one possible answer to the often raised question about functions and reasons for knotted structures in proteins.