Engineering allosteric control

The “wire”-like topology of sectors within protein molecules – linking active sites to distantly positioned surface sites – leads to a simple idea for the engineering of new allosteric communication between proteins. Specifically, can communication between the active sites of two otherwise unrelated proteins simply amount to physically approximating the distant sector-connected surface sites? Here, we show that indeed, naive connection of a plant light-sensing domain (LOV2) and a bacterial metabolic enzyme (DHFR) through their sector surfaces is sufficient to create weak but significant light-dependent enzymatic activity. In contrast, connection at a non-sector-connected surface site is not.

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