4wf2

Publication Abstract from PubMed

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 Escherichiacoli 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+/-0.3kcal/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.

Allosteric Coupling via Distant Disorder-to-Order Transitions.,Eginton C, Cressman WJ, Bachas S, Wade H, Beckett D J Mol Biol. 2015 Mar 4. pii: S0022-2836(15)00155-2. doi:, 10.1016/j.jmb.2015.02.021. PMID:25746672^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.