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J Mol Biol. 2015 Apr 24;427(8):1695-704. doi: 10.1016/j.jmb.2015.02.021. Epub 2015 Mar 4.

Allosteric coupling via distant disorder-to-order transitions.

Author information

1
Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA.
2
Department of Biophysics and Biophysical Chemistry, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
3
Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA. Electronic address: dbeckett@umd.edu.

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.

KEYWORDS:

allostery; coupled equilibria; disorder-to-order; protein:ligand interactions; protein:protein interactions

PMID:
25746672
DOI:
10.1016/j.jmb.2015.02.021
[Indexed for MEDLINE]

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