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SYSM: Symposium Topological constraints in biological and synthetic soft matter

SYSM 1: Topological constraints in biological and synthetic soft matter

SYSM 1.3: Invited Talk

Monday, September 27, 2021, 11:15–11:45, Audimax 1

Supercoiling in a Protein Increases its Stability — •Joanna Sulkowska and Szymon Niewieczerzał — Centre of New Technologies, University of Warsaw, Banacha 2c, 02-097 Warsaw, Poland

Currently it is known that at least 6% of proteins possess nontrivial topology (i.e. are entangled) and form structures called knots, slipknots, lassos, links and theta curves. A lasso is a structure that contains a covalent loop (closed by a cysteine, amide, or other bridge), crossed by at least one free end of a protein.

The supercoiling motif is the most complex type of nontrivial topology found in proteins with lasso motif. Based on a protein from extremophilic species with such a motif, with a coarse-grained protein model I will show that this protein can knot itself; however, the supercoiling changes a smooth landscape observed in reduced conditions into a two-state folding process in the oxidative conditions, with a deep intermediate state. The protein takes advantage of the hairpin-like motif to overcome the topological barrier and thus to supercoil. I will also show that the depth of the supercoiling motif, i.e. the length of the threaded terminus, has a crucial impact on the folding rates of the studied protein. Finally, I will show that fluctuations of the minimal surface area (i.e. the area of a surface spanned on a covalent loop) can be used to measure local stability, and that supercoiling motif introduces stability into the protein. These results suggest that the supercoiling motif enables the studied protein to live in physically extreme conditions, which are detrimental to most life on Earth.