An evolutionary bridge to a new protein fold

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

Research output: Contribution to journalArticlepeer-review

77 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
StatePublished - 2000

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Genetics


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