An evolutionary bridge to a new protein fold

Matthew Hj Cordes, Randall E. Burton, Nathan P. Walsh, C. James McKnight, Robert T. Sauer

Research output: Contribution to journalArticle

73 Scopus citations


Arc repressor bearing the N11L substitution (Arc-N11L) is an evolutionary intermediate between the wild type protein, in which the region surrounding position 11 forms a β-sheet, and a double mutant 'switch Arc', in which this region is helical. Here, Arc-N11L is shown to be able to adopt either the wild type or mutant conformations. Exchange between these structures occurs on the millisecond time scale in a dynamic equilibrium in which the relative populations of each fold depend on temperature, solvent conditions and ligand binding. The N11L mutation serves as an evolutionary bridge from the β-sheet to the helical fold because in the mutant, Leu is an integral part of the hydrophobic core of the new structure but can also occupy a surface position in the wild type structure. Conversely, the polar Asn 11 side chain serves as a negative design element in wild type Arc because it cannot be incorporated into the core of the mutant fold.

Original languageEnglish (US)
Pages (from-to)1129-1132
Number of pages4
JournalNature Structural Biology
Issue number12
Publication statusPublished - 2000
Externally publishedYes


ASJC Scopus subject areas

  • Biochemistry
  • Structural Biology
  • Genetics

Cite this

Cordes, M. H., Burton, R. E., Walsh, N. P., McKnight, C. J., & Sauer, R. T. (2000). An evolutionary bridge to a new protein fold. Nature Structural Biology, 7(12), 1129-1132.