We present a systems biology view on pseudoenzymes that acknowledges that genes are not selfish: the genome is. With network function as the selectable unit, there has been an evolutionary bonus for recombination of functions of and within proteins. Many proteins house a functionality by which they ‘read’ the cell's state, and one by which they ‘write’ and thereby change that state. Should the writer domain lose its cognate function, a ‘pseudoenzyme’ or ‘pseudosignaler’ arises. GlnK involved in Escherichia coli ammonia assimilation may well be a pseudosignaler, associating ‘reading’ the nitrogen state of the cell to ‘writing’ the ammonium uptake activity. We identify functional pseudosignalers in the cyclin-dependent kinase complexes regulating cell-cycle progression. For the mitogen-activated protein kinase pathway, we illustrate how a ‘dead’ pseudosignaler could produce potentially selectable functionalities. Four billion years ago, bioenergetics may have shuffled ‘electron-writers’, producing various networks that all served the same function of anaerobic ATP synthesis and carbon assimilation from hydrogen and carbon dioxide, but at different ATP/acetate ratios. This would have enabled organisms to deal with variable challenges of energy need and substrate supply. The same principle might enable ‘gear-shifting’ in real time, by dynamically generating different pseudo-redox enzymes, reshuffling their coenzymes, and rerouting network fluxes. Non-stationary pH gradients in thermal vents together with similar such shuffling mechanisms may have produced a first selectable proton-motivated pyrophosphate synthase and subsequent ATP synthase. A combination of functionalities into enzymes, signalers, and the pseudo-versions thereof may offer fitness in terms of plasticity, both in real time and in evolution.
An artistic model of the ‘molecular scissor’ ADAM10 (displayed in orange) at the cell surface, shown cleaving one of its substrates (green). ADAM10 is regulated by one of six TspanC8 tetraspanins (displayed in white or blue). The TspanC8s have distinct mechanisms of binding to ADAM10 and appear to dictate its substrate specificity. For more information, please see pages 719–730 in this issue of the Biochemical Society Transactions. Designer: Justyna Szyroka Artist: Eduardo Oliveira - Graphics Designer and Animator. Image kindly provided by Michael G Tomlinson.
Learning to read and write in evolution: from static pseudoenzymes and pseudosignalers to dynamic gear shifters
Abulikemu Abudukelimu, Thierry D.G.A. Mondeel, Matteo Barberis, Hans V. Westerhoff; Learning to read and write in evolution: from static pseudoenzymes and pseudosignalers to dynamic gear shifters. Biochem Soc Trans 15 June 2017; 45 (3): 635–652. doi: https://doi.org/10.1042/BST20160281
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