A historical perspective on protein crystallization from 1840 to the present day

Abstract

Protein crystallization has been known since 1840 and can prove to be straightforward but, in most cases, it constitutes a real bottleneck. This stimulated the birth of the biocrystallogenesis field with both ‘practical’ and ‘basic’ science aims. In the early years of biochemistry, crystallization was a tool for the preparation of biological substances. Today, biocrystallogenesis aims to provide efficient methods for crystal fabrication and a means to optimize crystal quality for X‐ray crystallography. The historical development of crystallization methods for structural biology occurred first in conjunction with 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, the identification of conditions that sustain crystal growth occurred mostly empirically but, in recent decades, this has moved progressively towards more rationality as a result of a deeper understanding of the physical chemistry of protein crystal growth and the use of idea‐driven screening and high‐throughput procedures. Protein and nucleic acid engineering procedures to facilitate crystallization, as well as crystallization methods in gelled‐media or by counter‐diffusion, represent recent important achievements, although the underlying concepts are old. The new nanotechnologies have brought a significant improvement in the practice of protein crystallization. Today, the increasing number of crystal structures deposited in the Protein Data Bank could mean that crystallization is no longer a bottleneck. This is not the case, however, because structural biology projects always become more challenging and thereby require adapted methods to enable the growth of the appropriate crystals, notably macromolecular assemblages.

XPA: A key scaffold for human nucleotide excision repair

“…X-ray crystallography in particular has realized a number of key developments including the shift to robotic systems for crystal screening, increased automation at synchrotron beamlines, and the availability of microfocus beamlines and FELs 108-110 . In addition, exciting recent advances in cryo-EM through the development of direct electron detectors, fast data acquisition, and protocols for tracking particle movement during data acquisition, are poised to revolutionize structural biology of NER incision complexes.…”

Hemoglobin Expression in Nonerythroid Cells: Novel or Ubiquitous?

“…He occasionally found small plate-like crystals in desiccated swine or human blood samples [1, 2]. These crystals were later named as “Haemoglobin” by Hoppe-Seyler in 1864 [3].…”

A brief history of macromolecular crystallography, illustrated by a family tree and its Nobel fruits

“…The subject of crystallization of proteins has been very recently discussed in a review in this journal [11] and thus is covered here only very briefly. It is not really possible to trace the first mention of crystals of macromolecules such as proteins, although the description of the serendipitously obtained 'blood crystals' of earthworm hemoglobin can be found in a book published as early as 1840 [12].…”