Disordered Motifs and Domains in Cell Control - October 11-15, 2014

Disordered Motifs and Domains in Cell Control

Poster Session II

37-POS Board 13 Intrinsically Disordered Ribonucleotide Reductase Inhibitors in S.cerevisiae Riccardo Marabini 1 , Sebastian S. Brøndum and Birthe B. Kragelund 1 1 Structural Biology and NMR Laboratory (SBiNLab), Department of Biology, University of Copenhagen, Denmark Ribonucleotide reductase (RNR) catalyzes the rate-limiting step in the deoxyribonucleotide biosynthesis pathway and it is an extremely important enzyme during DNA replication and damage. It is widely accepted that its dysregulation leads to unbalanced dNTPs levels in the cell and hence onset of mutations that ultimately can lead to various cancers. Recently, and in two different yeast strains ( S. cerevisiae and S.pombe) it has been demonstrated that a family of intrinsically disordered proteins (IDPs) exist that can inhibit RNR activity. Although RNR inhibition is believed to be common to these proteins their sequences diverge significantly and additional functions are suggested to be present and shared in subsets of these proteins. In this study we have used S.cerevisiae as a model organism and NMR spectroscopy as the main technique to delineate common structural and dynamical features of three RNR inhibitors, Sml1, Dif1 and Hug1. The aim is to identify common interaction motifs and key residues important for maintaining the disordered state. Through the description of the unfolded state, the disordered state and from functional characterization, we aim to address the protein non-folding problem.

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