The Promise and Challenge of High Pressure Macromolecular Crystallography

Abstract

Since its introduction in the early 1970s, high pressure crystallography (HPX) has shown great potential for the investigation of different types of matter. Using diamond anvil cells, HPX is an emerging technique that has been rapidly implemented, making it available to biologists, and there is immense potential for utilizing this technique in biological systems in the future. At the molecular level, high-pressure crystallographic investigation provides information on structural characteristics that not only determine the native conformation of a protein but also the conformations with higher free-energy, thus revealing function-related structural changes and properties that can be modified as a result of pressurization. The increase in the number of crystal structures of different macromolecules determined under high pressure over the last five decades can be ascribed mainly to two factors: the emergence of high-pressure cells with very large, open angles, and the advent of third generation synchrotron sources. The use of high pressure crystallography as a research tool has been shown to contribute to the advancements in the basic fields of biochemistry (protein misfolding and aggregation), biophysics (protein stability), and biotechnology (food processing). Presently, with a growing interest in biomedicine and nanotechnology, this nonstandard method appears to be a valid instrument for probing more challenging and complex systems. In this review, we present the method, highlight a selection of recent applications, and describe challenges for high pressure macromolecular crystallography (HPMX).