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Logo of jbcThe Journal of Biological Chemistry
J Biol Chem. 2015 April 10; 290(15): 9321.
PMCID: PMC4392239

Comparison of Evolutionary Rates of Structured and Disordered Proteins♦

Comparative Laboratory Evolution of Ordered and Disordered Enzymes

♦ See referenced article, J. Biol. Chem. 2015, 290, 9310–9320

Intrinsically disordered proteins are found in all life forms. They challenge the traditional view of proteins as entities with well-defined and distinct three-dimensional structures. One hypothesis suggests that disordered proteins help to shape protein evolution. In this Paper of the Week, a team led by Donald Hilvert at the ETH Zurich tested the hypothesis under controlled laboratory conditions. They took a structurally disordered variant of the enzyme dihydrofolate reductase (DHFR) from Escherichia coli and compared it with a more structured homolog from Bacillus stearothermophilus. The investigators used in vivo selection of the two enzymes in parallel, relying on DHFR activity as a measure of catalytic efficiency and evolution. They discovered that the two enzymes evolved more or less at the same rate even though the hypothesis proposes that disordered proteins evolve faster than ordered proteins. Although the DHFR variants accumulated distinctive mutations that affected their activity, their scaffolds did not change noticeably. The authors concluded, “Ordered and disordered enzymes can be similarly evolvable.”

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Location of mutations in the optimized DHFR variants relative to the sector of co-evolving residues in the DHFR family.

Articles from The Journal of Biological Chemistry are provided here courtesy of American Society for Biochemistry and Molecular Biology