Abstract
Two fundamental principles can account for how regulated networks of interacting proteins originated in cells. These are the law of mass action, which holds that the binding of one molecule to another increases with concentration, and the fact that the colocalization of molecules vastly increases their local concentrations. It follows that colocalization can amplify the effect on one protein of random mutations in another protein and can therefore, through natural selection, lead to interactions between proteins and to a startling variety of complex allosteric controls. It also follows that allostery is common and that homologous proteins can have different allosteric mechanisms. Thus, the regulated protein networks of organisms seem to be the inevitable consequence of natural selection operating under physical laws.
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Acknowledgements
We are grateful to A. K. Aggarwal, R. E. Dickerson, S. C. Harrison, L. N. Johnson, E. M. Marcotte, M. Robertson, W. E. Royer, M. Seeliger, D. E. Wemmer, C. Wolberger, T. O. Yeates and many other colleagues for comments. We thank S. Deindl, L. Leighton, W. E. Royer, D. E, Wemmer and X. Zhang for assistance with the figures. Support from the Howard Hughes Medical Institute, the National Institutes of Health, the US Department of Energy Office of Biological & Environmental Research, and the National Science Foundation is gratefully acknowledged.
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Correspondence should be addressed to the authors (david@mbi.ucla.edu; kuriyan@berkeley.edu).
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Kuriyan, J., Eisenberg, D. The origin of protein interactions and allostery in colocalization. Nature 450, 983–990 (2007). https://doi.org/10.1038/nature06524
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DOI: https://doi.org/10.1038/nature06524
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