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Liquid-like movements in crystalline insulin

Abstract

Diffuse X-ray scattering from protein crystals provides information about molecular flexibility and packing irregularities1–4. Here we analyse diffraction patterns from insulin crystals that show two types of scattering related to disorder: very diffuse, liquid-like diffraction, and haloes around the Bragg reflections. The haloes are due to coupled displacements of neighbouring molecules in the lattice, and the very diffuse scattering results from variations in atomic positions that are only locally correlated within each molecule. The measured intensity was digitally separated into three components: the Bragg reflections and associated haloes; the water and Compton scattering; and the scattering attributed to internal protein movements. We extend methods used to analyse disorder in membrane structures5–7 to simulate the diffuse scattering from crystalline insulin in terms of (1) the Patterson (autocorrelation) function of the ideal, ordered crystal structure, (2) the root-mean-square (r.m.s.) amplitude of the atomic movements, and (3) the mean distance over which these displacements are coupled. Move-ments of the atoms within the molecules, with r.m.s. amplitudes of 0.4–0.45 Å, appear to be coupled over a range of ~6 Å, as in a liquid. These locally coupled movements account for most of the disorder in the crystal. Also, the protein molecules, as a whole, jiggle in the lattice with r.m.s. amplitudes of ~0.25 Å that appear to be significantly correlated only between nearest neighbours.

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Caspar, D., Clarage, J., Salunke, D. et al. Liquid-like movements in crystalline insulin. Nature 332, 659–662 (1988). https://doi.org/10.1038/332659a0

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