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 I

22 – POS Board 22 Theoretical Model of a Knotted Protein VirC2 Bound to a Double Stranded Plasmid DNA

Mateusz Kurcinski , Andrzej Kolinski. University of Warsaw, Warsaw, Poland.

Agrobacterium tumefaciens ’s transfer system is the most common DNA delivery tool for genetic engineering of plants. Various researches suggest that VirC2 protein plays a crucial role in correct processing of the transfer DNA (T-DNA), however mechanism of its action remains unclear. The C-terminal domain of the VirC2 protein contains ribbon-helix-helix (RHH) motif, which is a common DNA-binding spot in transcription factors. Multiple experiments indicate that VirC2 binds to a double stranded plasmid DNA, but no direct evidence has been presented so far. Crystallographic structure revealed that VirC2 forms a trefoil knot in the DNA binding domain, within the RHH motif, although its role is yet to be determined. We developed a tool for modeling of protein-DNA complexes. It is based on the CABS [1] model, which has been successfully used in protein structure prediction, modeling of protein dynamics [2], investigation of folding mechanisms [3] and protein docking [4]. The model incorporates a reduced representation of molecules, a very efficient sampling scheme and a statistical force field. Because of that, CABS allows for simulation of large molecular systems, such as protein-DNA complexes in long molecular events, which is inaccessible for Molecular Dynamics based methods. In this work we present a theoretical model of interaction between VirC2 protein and a double stranded DNA molecule. The predicted structure of the complex may be helpful in understanding the role of the knot in the binding site and more generally the role of knots in proteins. [1] Kolinski, A., 2004, Acta Biochimica Polonica, 51(2), 349–71. [2] Jamroz, M., Kolinski, A. & Kmiecik, S., 2013, Nucleic Acids Research, 11, 1–5. [3] Kmiecik, S. & Kolinski, A., 2007, PNAS, 104(30), 12330–5. [4] Kurcinski, M., Kolinski, A. & Kmiecik, S., 2014, Journal of Chemical Theory and Computation, doi:10.1021/ct500287c

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