Protein crystallography from the perspective of technology developments

Abstract

Early on, crystallography was a domain of mineralogy and mathematics and dealt mostly with symmetry properties and imaginary crystal lattices. This changed when Wilhelm Conrad Röntgen discovered X-rays in 1895, and in 1912 Max von Laue and his associates discovered X-ray irradiated salt crystals would produce diffraction patterns that could reveal the internal atomic periodicity of the crystals. In the same year the father-and-son team, Henry and Lawrence Bragg successfully solved the first crystal structure of sodium chloride and the era of modern crystallography began. Protein crystallography (PX) started some 20 years later with the pioneering work of British crystallographers. In the past 50-60 years, the achievements of modern crystallography and particularly those in protein crystallography have been due to breakthroughs in theoretical and technical advancements such as phasing and direct methods; to more powerful X-ray sources such as synchrotron radiation (SR); to more sensitive and efficient X-ray detectors; to ever faster computers and to improvements in software. The exponential development of protein crystallography has been accelerated by the invention and applications of recombinant DNA technology that can yield nearly any protein of interest in large amounts and with relative ease. Novel methods, informatics platforms, and technologies for automation and high-throughput have allowed the development of large-scale, high efficiency macromolecular crystallography efforts in the field of structural genomics (SG). Very recently, the X-ray free-electron laser (XFEL) sources and its applications in protein crystallography have shown great potential for revolutionizing the whole field again in the near future.

Solid-phase synthesis and structural characterisation of phosphoroselenolate-modified DNA: a backbone analogue which does not impose conformational bias and facilitates SAD X-ray crystallography

“…17 The molecular biology techniques required to engineer polypeptide sequences containing a mutated selenomethionine residue have now become routine and as this residue does not disrupt protein folding, it is widely used in MAD (multiple wavelength anomalous dispersion) or SAD (single wavelength anomalous diffraction) applications. 18 Concurrent increased access to third generation synchrotron sources which generate more focussed, tunable X-rays of high brightness and stability coupled with automation of the screening of crystallisation conditions has engendered a considerable upsurge in protein crystal structure solution such that in the year 1990, 132 protein structures were deposited in the protein databank whereas in 2018 this number had risen to 10 306. Of the 137 000 protein crystal structures in the PDB repository by the end of 2018, over 10% had been solved using SAD or MAD methods.…”

Sample delivery using capillary and delivery medium for serial crystallography

“…Traditional X-ray crystallography has contributed greatly to biology, medicine, and industrial fields; [1][2][3] however, this method has certain experimental limitations, including radiation damage, cryogenic temperature, and static structural information. 4,5 This technique often produces biologically less relevant crystal structures, 6,7 but its limitations can be overcome by the serial crystallography (SX) technique.…”

Where is crystallography going?

“…1 indicates the timeline for some advances in MX. It is inevitably personal and many others have commented on these advances (see, for example, Su et al, 2015;Hendrickson, 2013). What we would stress is that structural analysis can impact discovery in biology in more than one way.…”