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

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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