Significance of Knotted Structures for Function of Proteins and Nucleic Acids - September 17-21, 2014

Significance of Knotted Structures for Function of Proteins and Nucleic Acids

Sunday Abstracts

Discoveries, Implications and Utilities of Proteins with Barriers, Knots, Slipknots, and Links Todd Yeates University of California, Los Angeles, USA Proteins have notoriously complex structures, and the routes by which they fold into such complex shapes remains an important and largely outstanding problem in biology. Proteins whose backbones have unusually complex topologies provide valuable model systems for exploring ideas related to folding mechanisms and landscapes, while also providing potentially valuable building blocks for creating interesting materials. Previous discoveries and new ideas will be discussed for proteins with diverse topological features.

Knotted Proteins under Tension Marek Cieplak . Institute of Physics, PAS, Warsaw, Poland.

We highlight the diversity of mechanical clamps, some of them topological in nature that have been found by making surveys of mechanostability of just under 20 000 proteins within structure-based models. The existence of superstable proteins (with the characteristic unfolding force in the range of 1000 pN) is predicted. In these studies, mechanostability has been assessed by stretching at constant speed. Here, we focus on stretching of knotted proteins at constant tension - the case which is more relevant biologically. In particular, we find that proteins with knots unravel in a way similar to those without knots: there is a crossover between the inverse Gaussian distribution of unfolding times at high forces to the exponential distribution at low forces. However, we observe that sudden jumps in the extension of a protein do not necessarily lead to jumps in the location of the ends of the knot and the knot can get fully tightened before the protein is stretched. We then propose a model to study the proteasome-induced protein translocation. It involves constant-force pulling through a funnel-shaped potential. We find that a) the process of translocation unfolds proteins bound for degradation efficiently, b) the tension along the protein backbone is non-uniform, and c) the stalling force is smaller than the force of puling by the proteasomal motor. Our results provide insights into the mechanisms of unfolding used by biological unfoldases and indicate that the experimental paradigm used for measuring the traction power of the proteasome Finally we discuss some aspects of folding of proteins with native knots.

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