RT Journal Article
SR Electronic
T1 Convergent Allostery in Ribonucleotide Reductase
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 504290
DO 10.1101/504290
A1 Thomas, William C.
A1 Brooks, F. Phil
A1 Burnim, Audrey A.
A1 Bacik, John-Paul
A1 Stubbe, JoAnne
A1 Kaelber, Jason T.
A1 Chen, James Z.
A1 Ando, Nozomi
YR 2018
UL http://biorxiv.org/content/early/2018/12/21/504290.abstract
AB Ribonucleotide reductases (RNRs) use a conserved radical-based mechanism to catalyze the conversion of ribonucleotides to deoxyribonucleotides. Within the RNR family, class Ib RNRs are notable for being largely restricted to bacteria, including many pathogens, and for lacking an evolutionarily mobile ATP-cone domain that allosterically controls overall activity. In this study, we report the emergence of a new and unexpected mechanism of activity regulation in the sole RNR of the model organism Bacillus subtilis. Using a hypothesis-driven structural approach that combines the strengths of small-angle X-ray scattering (SAXS), crystallography, and cryo-electron microscopy (cryo-EM), we describe the reversible interconversion of six unique structures, including a flexible, active tetramer and two novel, inhibited filaments. These structures reveal the conformational gymnastics necessary for RNR activity and the molecular basis for its control via an evolutionarily convergent form of allostery.