Allosteric Coupling via Distant Disorder-to-Order Transitions

作者：Eginton Christopher; Cressman William J; Bachas Sharrol; Wade Herschel; Beckett Dorothy^*

来源：Journal of Molecular Biology, 2015, 427(8): 1695-1704.

DOI：10.1016/j.jmb.2015.02.021

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

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. coil biotin repressor/biotin protein ligase) is achieved via reciprocal communication of disorder-to-order transitions on two distant functional surfaces.

• 出版日期2015-4-24