期刊
PROTEIN SCIENCE
卷 31, 期 12, 页码 -出版社
WILEY
DOI: 10.1002/pro.4483
关键词
allostery; evolution; evo-velocity; structure prediction
资金
- Cornell University
- National Science Foundation [MCB-1942668]
- Australian Research Council Centre of Excellence in Peptide and Protein Science [CE200100012]
- Australian Research Council Centre of Excellence in Synthetic Biology [CE200100029]
Ribonucleotide reductases (RNRs) are essential enzymes for DNA synthesis in all organisms. This study reveals the evolutionary relationships within the RNR family and identifies structurally similar domains and insertions with similar functions. These findings are important for understanding the diversification of the RNR family.
Ribonucleotide reductases (RNRs) are used by all free-living organisms and many viruses to catalyze an essential step in the de novo biosynthesis of DNA precursors. RNRs are remarkably diverse by primary sequence and cofactor requirement, while sharing a conserved fold and radical-based mechanism for nucleotide reduction. In this work, we expand on our recent phylogenetic inference of the entire RNR family and describe the evolutionarily relatedness of insertions and extensions around the structurally homologous catalytic barrel. Using evo-velocity and sequence similarity network (SSN) analyses, we show that the N-terminal regulatory motif known as the ATP-cone domain was likely inherited from an ancestral RNR. By combining SSN analysis with AlphaFold2 predictions, we also show that the C-terminal extensions of class II RNRs can contain folded domains that share homology with an Fe-S cluster assembly protein. Finally, using sequence analysis and AlphaFold2, we show that the sequence motif of a catalytically essential insertion known as the finger loop is tightly coupled to the catalytic mechanism. Based on these results, we propose an evolutionary model for the diversification of the RNR family.
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