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Doeke Hekstra

Doeke Hekstra

Seminar
Mon, Jan. 11, 2016, 3:15pm - 4:15pm
Frick Chemistry Laboratory, Taylor Auditorium
Host: Thomas Muir

Studying the mechanics of proteins with electric fields and X-rays.

The mechanics of proteins–the coordinated motions of amino acids and the pattern of forces constraining these motions–connect protein structure to function, as for macroscopic machines. One can characterize the mechanical workings of macroscopic machines by simply exerting forces at various specific positions and determining what moves together and how fast. Such an approach is currently not generally possible for proteins and other molecular machines. I will describe a new method combining the application of strong electric field pulses to protein crystals to exert precise patterns of force, with time-resolved crystallography to observe resulting motions in spatial and temporal detail. Using a PDZ domain as a model system, I show that protein crystals tolerate electric field pulses strong enough to drive concerted motions on the submicrosecond timescale. The induced motions are subtle, mechanistically diverse, and occur throughout the protein structure. The global pattern of electric field-induced motions is consistent with both local and allosteric conformational changes induced by ligand binding, including at conserved functional sites in the PDZ domain family. This work provides a path towards comprehensive experimental study of the mechanical basis of protein function.