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HUG Domain Is Responsible for Active Dimer Stabilization in an NrdJd Ribonucleotide Reductase
Tobias Fietze1, Piotr Wilk2,3, Florian Kabinger4
1Chair of Molecular Biotechnology, Technische Universität Dresden, Dresden 01217, Germany.
Biochemistry
|July 20, 2022
Summary
Ribonucleotide reductases (RNRs) require dimer formation for activity. A novel HUG domain in class II RNRs stabilizes this dimer, ensuring enzyme function even at low effector concentrations.
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Ribonucleotide reductases (RNRs) are essential enzymes catalyzing deoxyribonucleotide synthesis.
- Most RNRs require dimer formation of catalytic subunits for activity, with the active site at the interface.
- Regulatory mechanisms and substrate binding often involve interactions across the dimer interface.
Purpose of the Study:
- To identify and characterize a novel domain involved in catalytic dimer formation in class II RNRs.
- To elucidate the structural role of this domain in RNR function.
- To investigate the impact of this domain on enzyme activity and allosteric regulation.
Main Methods:
- 3D structure determination of the class II RNR from Rhodobacter sphaeroides using X-ray crystallography.
- Site-directed mutagenesis to genetically remove the identified HUG domain.
- Enzyme activity assays and dimerization capability assessments.
Main Results:
- A novel α-helical domain, termed the HUG domain, was identified at the dimer interface of class II RNRs.
- The HUG domain embraces the opposing subunit, playing a crucial role in dimer stabilization.
- Genetic removal of the HUG domain significantly reduced enzyme activity and dimerization capability.
- RNRs with the HUG domain exhibit reduced dependence on nucleotides for allosteric effector-mediated dimerization.
Conclusions:
- The HUG domain acts as an interlock, maintaining dimer integrity and RNR function under various conditions.
- This domain is critical for the stability and activity of class II RNRs.
- The HUG domain provides insights into the structural basis of RNR regulation and function.
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