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. 2015 Jul 3;40(3):308-328.
doi: 10.1179/0308018815Z.000000000120. Epub 2015 Dec 7.

Structural Biology: A Century-long Journey into an Unseen World

Stephen Curry  1
Affiliations

Structural Biology: A Century-long Journey into an Unseen World

Stephen Curry. Interdiscip Sci Rev. .

Abstract

When the first atomic structures of salt crystals were determined by the Braggs in 1912-1913, the analytical power of X-ray crystallography was immediately evident. Within a few decades the technique was being applied to the more complex molecules of chemistry and biology and is rightly regarded as the foundation stone of structural biology, a field that emerged in the 1950s when X-ray diffraction analysis revealed the atomic architecture of DNA and protein molecules. Since then the toolbox of structural biology has been augmented by other physical techniques, including nuclear magnetic resonance spectroscopy, electron microscopy, and solution scattering of X-rays and neutrons. Together these have transformed our understanding of the molecular basis of life. Here I review the major and most recent developments in structural biology that have brought us to the threshold of a landscape of astonishing molecular complexity.

Keywords: X-ray crystallography; biological macromolecules; electron microscopy; nuclear magnetic resonance spectroscopy; solution scattering.

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Figures

Figure 1
Figure 1
Protein crystallography: (a) detail of the X-ray diffraction pattern from a protein crystal, (b) an electron density map, with accompanying atomic model of a protein molecule. Bonds between atoms are shown as sticks, (c) the crystal structure of a protein-RNA complex. Protein and RNA chains are represented by ribbons and tubes respectively. Amino acids and nucleotides are also shown in stick representation (Colour images are available in the online version of this article).
Figure 2
Figure 2
NMR: (a) a 1D spectrum showing the proton (1H) chemical shifts recorded for a protein molecule, (b) a 2D spectrum showing the correlation of NMR chemical shifts between bonded 1H and 15N nuclei in a protein structure, (c) a best-fit ensemble of protein structures calculated from NMR data; for clarity only the protein backbone is shown.
Figure 3
Figure 3
Cryo-EM: (a) a cryo-electron micrograph of bacterial ribosomes, (b) class average images derived from averaging the images of ribosome particles determined to have the same orientation, (c) a high-resolution 3D reconstruction of the ribosome. Images are adapted from Bai et al. 2013 under the terms of a Creative Commons 3.0 Attribution Licence
Figure 4
Figure 4
Molecular structures and the molecular sociology of the cell: (a) interaction between the foot-and-mouth disease 3C protease and a peptide it is about to cleave (PDB ID 2wv4) (Zunszain et al. 2010), (b) structure of tomato aspermy virus protein 2b bound to and neutralizing the antiviral effect of a cellular double-stranded RNA molecule (PDB ID 2zi0) (Chen et al. 2008), (c) close-up view of the ribosome, the gigantic RNA-protein machine that synthesizes proteins found in all cells (PDB ID 4v88) (Ben-Shem et al. 2011), (d) detail from a still from the animation ‘Chromosome and Kinetochore’. (https://youtu.be/0JpOJ4F4984) showing the kinetochore and associated microtubules, a complex system of molecules that separates duplicated chromosomes just prior to cell division.
See this image and copyright information in PMC

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