2012/11/16

Glucose-galactose binding protein: e pur si muove.

Protein function is often coupled to internal dynamics. Periplasmic binding proteins are bi-domain bacterial proteins that can recognize many different nutrients and oligoelements, required for the survival of the organism. They constitute a beautiful example of functional dynamics since they trap the substrate in the clef between the two domains, producing a significant conformational rearrangement of the two protein moieties ("Venus flytrap mechanism"). Investigators of the Structural Biology Unit from CICbioGUNE have studied the binding mechanism in two of these periplasmic proteins that have unrelated sequences but are structurally homologous, using high resolution NMR spectroscopy. Their results show that ribose binding protein binds the monosaccharide following an induced fit mechanism while glucose-galactose binding protein employs conformational selection. Site directed mutagenesis and structural analyses were used to demonstrate that the hinge region is the ultimate (and only) responsible for such allosteric motions.

There is a persistent great interest in developing efficient and sensitive methods to monitor glucose levels in diabetes patients, a severe chronic condition that affects over 100 million people worldwide. The conformational rearrangement associated to the binding of glucose to periplasmic proteins has been suggested to be exploited in the design of glucose biosensors. The new study, published in the Journal of the American Chemical Society, suggests a novel way for reducing the ligand affinity without affecting its specificity, by exploiting the coupling between hinge composition and apparent ligand affinity and paves the way for the design of a novel generation of nanoscopic glucose biosensors.