Direct observation of structure-function relationship in motor proteins

Siv Schwink

[image:24753 class:fright]The relationship between protein structure and function is essential in determining mechanism, yet most techniques do not provide a direct measurement of this relationship. The Ha and Chemla labs recently developed a combined optical trap-fluorescence microscope that allows for measurements of structure and function simultaneously. In Comstock, M. J. et al., (2015) Science 348(6232):352-4, they applied this approach to the DNA repair helicase UvrD, showing for the first time how two distinct types of unwinding activity are regulated by its stoichiometry, and how two structural states termed ‘open’ and ‘closed’, the function of which have been debated for years, control its directionality of translocation relative to the DNA fork junction. In a companion study (Arslan, S. et al. (2015) Science 348(6232):344-7), the team engineered homologs of UvrD, locking them into each structural state by intermolecular cross-linking. Locking into the closed conformation turns the proteins into “superhelicases” capable of unwinding DNA over a great distance and against large forces. These findings point to mechanisms by which conformational states control activity and by which these states are regulated in the cell to promote certain functions. Moreover, the ability to bioengineer molecules to perform specific tasks holds promise for applications such as rapid DNA sequencing.