Convergent allostery in ribonucleotide reductase

Area of Science:

• Biochemistry
• Structural Biology
• Microbiology

Background:

• Ribonucleotide reductases (RNRs) are essential enzymes catalyzing deoxyribonucleotide synthesis via a radical mechanism.
• Class Ib RNRs, prevalent in bacteria and pathogens, lack the typical ATP-cone allosteric control domain.
• Bacillus subtilis possesses a unique RNR system, distinct from other bacterial homologs.

Purpose of the Study:

• To elucidate the distinct mechanism of activity regulation in the Bacillus subtilis RNR.
• To characterize the structural basis of RNR regulation in the absence of the canonical ATP-cone domain.
• To investigate the conformational dynamics governing RNR function and allosteric control.

Main Methods:

• Utilized a hypothesis-driven structural biology approach.
• Employed small-angle X-ray scattering (SAXS) to study enzyme structure in solution.
• Integrated crystallography and cryo-electron microscopy (cryo-EM) for high-resolution structural determination.

Main Results:

• Identified six unique interconverting structures of the Bacillus subtilis RNR.
• Observed a flexible active tetrameric state and two distinct inhibited helical filament states.
• Revealed a novel, evolutionarily convergent allosteric mechanism for RNR regulation.

Conclusions:

• The Bacillus subtilis RNR employs a unique structural mechanism for activity regulation.
• Conformational flexibility and interconversion between states are critical for RNR function.
• This study uncovers a new paradigm for allosteric control in bacterial RNRs.