Allosteric coupling via distant disorder-to-order transitions

Christopher Eginton, William J. Cressman, Sharrol Bachas, Herschel Wade, Dorothy Beckett

Research output: Contribution to journalArticlepeer-review

Abstract

Intrinsic disorder provides a means of maximizing allosteric coupling in proteins. However, the mechanisms by which the disorder functions in allostery remain to be elucidated. Small ligand, bio-5′-AMP, binding and dimerization of the Escherichia coli biotin repressor are allosterically coupled. Folding of a disordered loop in the allosteric effector binding site is required to realize the full coupling free energy of-4.0 ± 0.3 kcal/mol observed in the wild-type protein. Alanine substitution of a glycine residue on the dimerization surface that does not directly contribute to the dimerization interface completely abolishes this coupling. In this work, the structure of this variant, solved by X-ray crystallography, reveals a monomeric corepressor-bound protein. In the structure loops, neither of which contains the alanine substitution, on both the dimerization and effector binding surfaces that are folded in the corepressor-bound wild-type protein are disordered. The structural data combined with functional measurements indicate that allosteric coupling between ligand binding and dimerization in BirA (E. coli biotin repressor/biotin protein ligase) is achieved via reciprocal communication of disorder-to-order transitions on two distant functional surfaces.

Original languageEnglish (US)
Pages (from-to)1695-1704
Number of pages10
JournalJournal of molecular biology
Volume427
Issue number8
DOIs
StatePublished - 2015

Keywords

  • Allostery
  • Coupled equilibria
  • Disorder-to-order
  • Protein: ligand interactions
  • Protein: protein interactions

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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