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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