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BP: Fachverband Biologische Physik

BP 30: Protein Structure and Dynamics

BP 30.5: Hauptvortrag

Donnerstag, 20. März 2025, 16:00–16:30, H46

Topology in biological matter - are there double knots in proteins or maybe even more complicated knots? Prediction and in vitro verification. — •Joanna I Sulkowska — University of Warsaw, Banacha 2C, 02-097, Poland

We have been aware of the existence of knotted proteins for over 30 years-but it is challenging to predict what is the most complicated not that can be formed in proteins. Recently, based on AlphaFold (AF) method we predicted new and the most complex knotted topologies recorded to date - double trefoil knots (see AlphaKnot database). We found five domain arrangements that result in a doubly knotted structure in almost a thousand proteins. The double knot topology is found in knotted membrane proteins from the CaCA family, that functions as ion transporters, in the group of carbonic anhydrases that catalyze the hydration of carbon dioxide, and in the proteins from the SPOUT superfamily that gathers 31 knotted methyltransferases with the active site-forming knot.

Herein, I will present the first crystal structure of a double knotted protein TrmD-Tm1570 from Calditerrivibrio nitroreducens from SPOUT superfamily. The protein consists of two domains TrmD and Tm1570, each embedding a single trefoil knot, which can function on their own. We show that it folds in vitro and is biologically active.

I will also explain how AF and AI methods can be used to design artificially knotted proteins that can be obtained in vitro. This shows that AF, while predicting structure, also takes into account folding and overcoming a non-trivial looping pathway.

Keywords: topology; protein structure prediction; new folds; folding pathway