Coupling ligand recognition to protein folding in an engineered variant of rabbit ileal lipid binding protein

Abstract

We have engineered a variant of the β-clam shell protein ILBP which lacks the α-helical motif that caps the central binding cavity; the mutant protein is sufficiently destabilised that it is unfolded under physiological conditions, however, it unexpectedly binds its natural bile acid substrates with high affinity forming a native-like β-sheet rich structure and demonstrating strong thermodynamic coupling between ligand binding and protein folding.