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From words to literature in structural proteomics

Abstract

Technical advances on several frontiers have expanded the applicability of existing methods in structural biology and helped close the resolution gaps between them. As a result, we are now poised to integrate structural information gathered at multiple levels of the biological hierarchy — from atoms to cells — into a common framework. The goal is a comprehensive description of the multitude of interactions between molecular entities, which in turn is a prerequisite for the discovery of general structural principles that underlie all cellular processes.

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Figure 1: Illustration of the size range of biomolecular structures solved by X-ray crystallography and the size distribution of structures contained in the Protein Quaternary Structure (PQS) database (http://pqs.ebi.ac.uk).
Figure 2: Docking the atomic model of tubulin into the cryo-EM density map of the assembled microtubule.
Figure 3: Representative example that illustrates the type of 3D reconstructions that can be obtained with large macromolecular complexes by single-particle cryo-EM.
Figure 4: Experimental and theoretical methods that can provide information about a macromolecular assembly structure.
Figure 5: Hybrid approaches to structure determination of macromolecular complexes.
Figure 6: Principle of electron tomography.
Figure 7: Mapping the spatial distribution of complexes and their interactions within cells.

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Acknowledgements

We thank N. Eswar for preparing the histograms in Fig. 1, M. Simon, B. Jap and H. Noller for permission to use the structural images in Fig. 1, K. H. Downing for Fig. 2, B. Rockel for Fig. 3, and F. Alber for Figs 4 and 5a. We are also grateful to P. Bjorkman and H. Moss for commenting on the manuscript. This work has been supported in part by NIH grants (to A.S., R.M.G. and T.E.), the Agouron Institute (T.E.) and a Max-Planck Research Award (W.B.).

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Sali, A., Glaeser, R., Earnest, T. et al. From words to literature in structural proteomics. Nature 422, 216–225 (2003). https://doi.org/10.1038/nature01513

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