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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