PT  - JOURNAL ARTICLE
AU  - Thomas, William C.
AU  - Brooks, F. Phil
AU  - Burnim, Audrey A.
AU  - Bacik, John-Paul
AU  - Stubbe, JoAnne
AU  - Kaelber, Jason T.
AU  - Chen, James Z.
AU  - Ando, Nozomi
TI  - Convergent Allostery in Ribonucleotide Reductase
AID  - 10.1101/504290
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 504290
4099  - http://biorxiv.org/content/early/2018/12/21/504290.short
4100  - http://biorxiv.org/content/early/2018/12/21/504290.full
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.