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 Citations (Scopus)

Abstract

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
Volume7
Issue number12
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Bearings (structural)
Conformations
Substitution reactions
Switches
Ligands
Mutation
Temperature
Population
Proteins

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. https://doi.org/10.1038/81985

An evolutionary bridge to a new protein fold. / Cordes, Matthew Hj; Burton, Randall E.; Walsh, Nathan P.; McKnight, C. James; Sauer, Robert T.

In: Nature Structural Biology, Vol. 7, No. 12, 2000, p. 1129-1132.

Research output: Contribution to journalArticle

Cordes, MH, Burton, RE, Walsh, NP, McKnight, CJ & Sauer, RT 2000, 'An evolutionary bridge to a new protein fold', Nature Structural Biology, vol. 7, no. 12, pp. 1129-1132. https://doi.org/10.1038/81985
Cordes MH, Burton RE, Walsh NP, McKnight CJ, Sauer RT. An evolutionary bridge to a new protein fold. Nature Structural Biology. 2000;7(12):1129-1132. https://doi.org/10.1038/81985
Cordes, Matthew Hj ; Burton, Randall E. ; Walsh, Nathan P. ; McKnight, C. James ; Sauer, Robert T. / An evolutionary bridge to a new protein fold. In: Nature Structural Biology. 2000 ; Vol. 7, No. 12. pp. 1129-1132.
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