hahn lab

loopology



Domains conferring either photo-inhibition (LOV2) or activation induced by small molecules (uniRapR) are inserted at allosteric sites away from the active sites. The "loopology" approach identifies "tight loops" on the surface that are allosterically coupled to the active site, and that can be controled through insertion of engineered domains.


LOV is photoactivated very rapidly (< 0.5 milliseconds). The half time for return to the dark state can be adjusted using point mutations (in our hands from 1.7 to 496 seconds, Curr. Protoc. Cell Biol., 73: 21.10.1-14, 2016). Rapid return times are useful for precise kinetic control. Slower return times enable continuous activation with only a brief pulse of light every few minutes.


Description of the approach

Dagliyan, O., Tarnawski, M., Chu, P-H., Shirvanyants, D., Schlichting, I., *Dokholyan, N.V., and *Hahn, K.M. Engineering extrinsic disorder to control protein activity in living cells.  Science, 354(6318): 1441-1444, 2016. PMC5362825. View free in Science online: Full text & PDF | Free PMC article

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