Author: ["Doeke R. Hekstra","K. Ian White","Michael A. Socolich","Robert W. Henning","Vukica Šrajer","Rama Ranganathan"]
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Abstract
The internal mechanics of proteins—the coordinated motions of amino acids and the pattern of forces constraining these motions—connects protein structure to function. Here we describe a new method combining the application of strong electric field pulses to protein crystals with time-resolved X-ray crystallography to observe conformational changes in spatial and temporal detail. Using a human PDZ domain (LNX2PDZ2) as a model system, we show that protein crystals tolerate electric field pulses strong enough to drive concerted motions on the sub-microsecond timescale. The induced motions are subtle, involve diverse physical mechanisms, and occur throughout the protein structure. The global pattern of electric-field-induced motions is consistent with both local and allosteric conformational changes naturally induced by ligand binding, including at conserved functional sites in the PDZ domain family. This work lays the foundation for comprehensive experimental study of the mechanical basis of protein function. A new method in which strong electric fields are applied to a protein crystal while collecting time-resolved X-ray diffraction patterns is able to follow the mechanical motions of all the constituent atoms, with implications for molecular biology and drug discovery. X-ray crystallography can reveal the three-dimensional structures of large proteins at atomic resolution, but provides only a static view. Now Rama Ranganathan and colleagues have applied strong electric fields to a protein crystal while collecting time-resolved X-ray diffraction patterns, to follow the mechanical motions of all constituent atoms—the essence of how machine-like proteins work. Of direct interest to molecular biology and drug discovery, this approach to protein mechanics should also inspire physicists in materials science and electrical engineering.Cite this article
Hekstra, D., White, K., Socolich, M. et al. Electric-field-stimulated protein mechanics. Nature 540, 400–405 (2016). https://doi.org/10.1038/nature20571 