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

Friday Abstracts

Untying a Protein Knot - Translocation of Knotted Proteins through a Pore Piotr Szymczak . University of Warsaw, Warsaw, Poland. In less than 1% of proteins the polypeptide chain adopts a knotted configuration. What is it then about the knotted proteins that makes them so rare in living matter? One possibility, proposed in [1-3] is that the presence of a knot may affect the ability of proteins to be degraded in proteasome or translocated through the membranes. The smallest constrictions in the mitochondrial pores or proteasome openings are 12-14 Angstrom in diameter, too narrow to accommodate folded structures, thus translocation must be coupled to protein unfolding. Unfolding and import of proteins into mitochondria or proteasome are facilitated by molecular motors acting with the forces of the order of 30pN. However, as shown in [2,4-5], the protein knots tend to tighten under the action of the force. The radius of gyration of the tight knot is about 7-8 Angstroms for a trefoil, which means that the knot seems to be a shade too large to squeeze through the pore openings. This leaves us with two possibilities: either the knot diffuses towards the end of the chain and slides away or gets tightened and jams the opening [3]. We report the result of molecular dynamics simulations of protein translocation demonstrating topological traps might be prevented by using a pulling protocol of a repetitive, on-off character. Such a repetitive pulling is biologically relevant, since the mitochondrial import motor, like other ATPases, transforms chemical energy into directed motions via nucleotide-hydrolysis-mediated conformational changes, which are cyclic in character.

[1] P. Virnau et al., PLoS Comput. Biol. 2(9), e122 (2006) [2] T. Bornschloegl et al, Biophys. J., 96, 1508 (2009) [3] P. Szymczak, Biochem. Soc. Trans. 41, 620 (2013) [4] J. Sulkowska et al, Phys. Rev. Lett. 100, 058106 (2008) [5] J. Dzubiella, Biophys. J. 96, 831 (2009)

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