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The molecular sociology of the cell

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Abstract

Proteomic studies have yielded detailed lists of the proteins present in a cell. Comparatively little is known, however, about how these proteins interact and are spatially arranged within the 'functional modules' of the cell: that is, the 'molecular sociology' of the cell. This gap is now being bridged by using emerging experimental techniques, such as mass spectrometry of complexes and single-particle cryo-electron microscopy, to complement traditional biochemical and biophysical methods. With the development of integrative computational methods to exploit the data obtained, such hybrid approaches will uncover the molecular architectures, and perhaps even atomic models, of many protein complexes. With these structures in hand, researchers will be poised to use cryo-electron tomography to view protein complexes in action within cells, providing unprecedented insights into protein-interaction networks.

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Figure 1: A polypeptide-chain model for a clathrin D6 barrel.
Figure 2: Determining an atomic model of the yeast RNA exosome, by using mass spectrometry and comparative protein-structure modelling.
Figure 3: The molecular architecture of the 26S proteasome.
Figure 4: The molecular architecture of the NPC.
Figure 5: Integrative structure determination.
Figure 6: Mapping of 70S ribosomes in a tomogram of the bacterium Spiroplasma melliferum80.

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Acknowledgements

We thank F. Alber, F. Foerster, M. Topf, D. Devos, J. Aitchison, C. Akey, M. Rout, B. Chait, R. Russell, H. Hernández, D. Matak-Vinkovic, M. Sharon, T. Taverner, J. Ortiz and S. Nickell. We also thank R. M. Glaeser for critical review of the manuscript. We are grateful to C. Johnson, S. Parker, C. Scheidegger and C. Silva of the Scientific Computing and Imaging Institute (University of Utah), and to R. K. Morley of RayScale, for help with preparing some of the images. We acknowledge funding from Interaction Proteome and 3D Repertoire (both funded by the European Commission), the Forum for European Structural Proteomics, the National Institutes of Health and the National Science Foundation.

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Correspondence should be addressed to the authors (cvr24@cam.ac.uk; sali@salilab.org; baumeist@biochem.mpg.de).

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Robinson, C., Sali, A. & Baumeister, W. The molecular sociology of the cell. Nature 450, 973–982 (2007). https://doi.org/10.1038/nature06523

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