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The origin of protein interactions and allostery in colocalization

Nature volume 450, pages 983–990 (2007)Cite this article

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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Figure 1: The evolution of interacting proteins and allostery by single mutations.
Figure 2: The effect of colocalization on binding.
Figure 3: Examples of fused protein domains in one organism that are homologous to separate domains in another organism.
Figure 4: Assemblies of homeodomain-containing proteins and haemoglobin.
Figure 5: Mechanisms of control by phosphorylation.
Figure 6: Diverse regulatory mechanisms in tyrosine kinases.

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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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  1. Department of Molecular and Cell Biology and Department of Chemistry, Howard Hughes Medical Institute, California Institute for Quantitative Biosciences, University of California, Berkeley, 94720, California, USA

    John Kuriyan

  2. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, 94720, California, USA

    John Kuriyan

  3. University of California at Los Angeles–Department of Energy Institute of Genomics and Proteomics, Department of Biological Chemistry, and Department of Chemistry and Biochemistry, Howard Hughes Medical Institute, Institute of Molecular Biology, University of California, Los Angeles, 90095, California, USA

    David Eisenberg

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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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