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Dynamic personalities of proteins

Abstract

Because proteins are central to cellular function, researchers have sought to uncover the secrets of how these complex macromolecules execute such a fascinating variety of functions. Although static structures are known for many proteins, the functions of proteins are governed ultimately by their dynamic character (or 'personality'). The dream is to 'watch' proteins in action in real time at atomic resolution. This requires addition of a fourth dimension, time, to structural biology so that the positions in space and time of all atoms in a protein can be described in detail.

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Figure 1: The energy landscape defines the amplitude and timescale of protein motions.
Figure 2: Microsecond-to-millisecond protein dynamics are necessary for catalysis and are an intrinsic property of CYPA as shown by NMR relaxation dispersion experiments.
Figure 3: Single-molecule FRET reveals ordered, stepwise rotation of F0F1-ATP synthase on the millisecond timescale during ATP hydrolysis and synthesis.
Figure 4: Time dependence of carbon-monoxide migration and corresponding structural relaxation in myoglobin, using picosecond time-resolved X-ray crystallography.
Figure 5: The role of protein dynamics in molecular recognition by calmodulin on a range of timescales.
Figure 6: Ion-channel selectivity investigated by X-ray crystallography and molecular-dynamics simulations.
Figure 7: A hierarchy of protein dynamics in space and time underlies enzyme catalysis, using the enzyme adenylate kinase as an example.

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Acknowledgements

We thank M. Börsch, P. Anfinrud and B. Roux for providing the original images of Figs 3, 4 and 6b.

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Correspondence should be addressed to D.K. (dkern@brandeis.edu).

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Henzler-Wildman, K., Kern, D. Dynamic personalities of proteins. Nature 450, 964–972 (2007). https://doi.org/10.1038/nature06522

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