A protein that dramatically alters its shape could have implications in fields ranging from new materials to drug design.

Neil Thomas, Mark Searle and colleagues at the University of Nottingham, UK, have made a variant of ileal lipid binding protein (ILBP) that is unfolded in solution, but forms a compact folded structure when it binds to a ligand.

Structure of rabbit ILBP (left) and folded variant lacking the cap (right)

The team made the variant while trying to widen the range of ligands for ILBP by removing the cap over its binding cavity. They found that their altered protein, called -ILBP, did not have the usual folded 3D structure, but instead formed a flexible globule. When a ligand molecule was added, the protein folded around it to form a structure very similar to the native protein.

Protein function is closely linked to changes in structure and energy caused when a ligand binds. The way that -ILBP folds up around its ligand is an extreme example of this effect, said Dudley Williams, an expert in ligand-protein interactions, at the University of Cambridge, UK. 'Since the ligand-induced tightening of a protein structure can increase ligand affinity, the tightening of enzyme structures in the transition state can explain the apparent magic of [enzyme] catalysis,' said Williams.

'Our understanding of weak, non-covalent interactions in molecular recognition underpins biology, supramolecular chemistry and materials science,' said Searle. 'The ability of a small ligand to induce large conformational changes in a protein has potential applications in the biosensor field and in engineering proteins [with] novel catalytic properties,' he said.

James Mitchell Crow

This article has been updated (08 December 2006):  the protein discussed is not an enzyme but a carrier protein, and the related binding molecules ligands not substrates.