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Even if imprisoned inside a crystal, molecules can still move

Grenoble / Jülich, 5 October 2015 – X-ray crystallography reveals the three-dimensional structure of a molecule, thus making it possible to understand how it works and potentially use this knowledge to subsequently modulate its activity, especially for therapeutic or biotechnological purposes. For the first time, a study has shown that residual movements continue to animate proteins inside a crystal and that this movement “blurs” the structures obtained via crystallography. The study stresses that the more these residual movements are restricted, the better the crystalline order. That is why molecules consisting of the most compact crystals generally make it possible to obtain structures of better quality. This research combines crystallography, nuclear magnetic resonance (NMR) and simulation and is the result of an international cooperation involving researchers from the Institute of Structural Biology (ISB, CEA/CNRS/ Joseph Fourier University) in Grenoble, France, Purdue University, USA, and the Institute of Complex Systems (ICS-6: Structural Biochemistry) at Forschungszentrum Jülich in Germany. The results were published in Nature Communications.

X-ray crystallography is the most prolific method for determining protein structures. The quality of a crystallographic structure depends on the “degree of order” within the crystal. Proteins are generally only a few nanometres in size. Several thousand billion protein molecules must perfectly fit together in order to create a well-ordered crystalline structure in three dimensions. This stage is necessary if a structure is to be successfully obtained. Sometimes crystals, which may appear macroscopically perfect, disintegrate if subjected to X-rays, thus destroying their structure. It has been suggested that mass movements of crystalline proteins might explain this paradox, but this supposedly slow residual dynamic had never been observed directly in a crystal.

The researchers at IBS used a multi-technique approach, combining solid-state NMR spectroscopy, simulations of molecular dynamics and X-ray crystallography. Thanks to solid-state NMR, they were able to measure the dynamics of a model protein, ubiquitin, in three of its crystalline forms. Their results indicate that, even when crystallised, proteins continue to produce slight residual movements. The less compact the crystal, the more unrestrained the movements within it.

Accordingly, crystallographic data collected for three types of crystal indicate that the more compact the crystal, the better it defracts, making it easier to determine the structure of the proteins of which it consists. To reconstitute the movement of proteins in these crystalline networks, simulations of molecular dynamics were performed for each of the three crystalline forms. These simulations suggest that, within crystals, proteins revolve around each other a few degrees at microsecond speed. As shown through NMR measurements, this swinging motion" is greater the less compact the crystal.

Zoom ins KristallgitterThis study contributes to a better understanding of how slow molecular movements affect the quality of crystallographic structures as well as, more generally, the dynamic of molecules on an atomic scale. It also partially explains why certain crystals, while they may look “fine” macroscopically, reveal themselves to be lacking information when studied through crystallography.
Copyright: Paul Schanda/CEA

Original publication:
Peixiang Ma et al.: Observing the overall rocking motion of a protein in a crystal. Nature Communications, October 5, 2015, DOI: 10.1038/ncomms9361


Prof. Dr. Dieter Willbold
Institute of Complex Systems, Structural Biochemistry (ICS-6)
Forschungszentrum Jülich
Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf
Tel.: +49 2461 61-2100

Dr. Paul Schanda
Institut de Biologie Structurale. Grenoble, France
Tel.: +33 457 428-659

Press contact:

Peter Zekert
Institute of Complex Systems, Structural Biochemistry (ICS-6)
Tel.: +49 (0) 2461 61-9711