A historical perspective on protein crystallization from1840 to the present day

摘要

Protein crystallization has been known since 1840 and can prove to bestraightforward but, in most cases, it constitutes a real bottleneck. This stimulatedthe birth of the biocrystallogenesis field with both ‘practical’ and‘basic’ science aims. In the early years of biochemistry, crystallization was atool for the preparation of biological substances. Today, biocrystallogenesisaims to provide efficient methods for crystal fabrication and a means to optimizecrystal quality for X-ray crystallography. The historical development ofcrystallization methods for structural biology occurred first in conjunctionwith that of biochemical and genetic methods for macromolecule production,then with the development of structure determination methodologies and,recently, with routine access to synchrotron X-ray sources. Previously, theidentification of conditions that sustain crystal growth occurred mostlyempirically but, in recent decades, this has moved progressively towardsmore rationality as a result of a deeper understanding of the physical chemistryof protein crystal growth and the use of idea-driven screening and highthroughputprocedures. Protein and nucleic acid engineering procedures tofacilitate crystallization, as well as crystallization methods in gelled-media orby counter-diffusion, represent recent important achievements, although theunderlying concepts are old. The new nanotechnologies have brought a significantimprovement in the practice of protein crystallization. Today, theincreasing number of crystal structures deposited in the Protein Data Bankcould mean that crystallization is no longer a bottleneck. This is not the case,however, because structural biology projects always become more challengingand thereby require adapted methods to enable the growth of the appropriatecrystals, notably macromolecular assemblages.