Significance of Knotted Structures for Function of Proteins and Nucleic Acids
Poster Session II
34 – POS
Board 6
Folding Knotted Proteins in a Chaperonin Cage
Szymon Niewieczerzał
1
and Joanna I. Sulkowska
1,2
1
Centre of New Technologies, University of Warsaw, Banacha 2c, Warsaw, Poland.
2
Faculty of
Chemistry, University of Warsaw, Pasteura 1, Warsaw, Poland
Thermodynamic properties of middle size knotted proteins are still not known. Recent results
have shown that it is possible to determine the free energy landscape of the smallest knotted
protein, MJ0366 from Methanocaldococcus jannaschii, with structure based models [1]. On the
other hand, recent experimental results have shown that also bigger protein with much deeper
knot, YibK, can tie itself, also observed with numerical simulations, however chaperonin-
assisted folding can significantly speed this process up.
In this work we examine by molecular dynamics with structures based model of the chaperonin-
assisted folding and thermodynamics of MJ0366, and its version with the extended C-terminal
tail. We find out that assisted folding significantly increase probability of knotting. Moreover,
the size of the confinement has a significant impact on the kinetics of folding-unfolding
processes, which was also previously reported for proteins with an unknoted topology.
Introduction of attraction forces between cavity walls and the protein shifts the equillibrium
towards the denaturated state. Independently of an available space for the protein, hysteretic
behavior is observed in folding-unfolding processes. Surprisingly the unknotting (not only
unfolding) occurs at the presence of a larger fraction of native contacts (Q) than knotting (and
folding). Those results suggest that chaperonin cage could have a significant influence on
knotting probability for middle size proteins as was suggested experimentally for YibK [2].
1. Noel JK, Onuchic JN, Sulkowska JI (2013), “Knotting a protein in explicit solvent”, The
Journal of Physical Chemistry Letters, 4(21), 3570-3573.
2. Mallam AL, Jackson SE (2011), “Knot formation in newly translated proteins is spontaneous
and accelerated by chaperonins”, Nat Chem Biol 8:147–153
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