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Nature 450, 983-990 (13 December 2007) | doi:10.1038/nature06524; Published online 12 December 2007

Review Article The origin of protein interactions and allostery in colocalization

John Kuriyan1,2 & David Eisenberg3

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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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