All living organisms include a set of signaling devices that confer the ability to dynamically perceive and adapt to the fluctuating environment. Two-component systems are part of this sensory machinery that regulates the execution of different genetic and/or biochemical programs in response to specific physical or chemical signals. In the last two decades, there has been tremendous progress in our molecular understanding on how signals are detected, the allosteric mechanisms that control intramolecular information transmission and the specificity determinants that guarantee correct wiring. All this information is starting to be exploited in the development of new synthetic networks. Connecting multiple molecular players, analogous to programming lines of code, can provide the resources to build new sophisticated biocomputing systems. The Synthetic Biology field is starting to revolutionize several scientific fields, such as biomedicine and agriculture, propelling the development of new solutions. Expanding the spectrum of available nanodevices in the toolbox is key to unleash its full potential. This review aims to discuss, from a structural perspective, how to take advantage of the vast array of sensor and effector protein modules involved in two-component systems for the construction of new synthetic circuits.
In this issue Byrne and colleagues (pp. 141–160) confirm that, as predicted, PSKH2 lacks detectable protein phosphotransferase activity, and exploit structural informatics, biochemistry and cellular proteomics to begin to characterise vertebrate PSKH2 orthologues. They show that PSKH2 is part of a cellular mitochondrial protein network, and that its expression is regulated through client-status within the HSP90/Cdc37 molecular chaperone system. The cover image shows an Alpha Fold 2 model of human PSKH2 (grey, green and brown) bound to HSP90 (cyan) and Cdc37 (magenta). The image is courtesy of Patrick Eyers.
Structural features of sensory two component systems: a synthetic biology perspective
Marcos Nieves, Alejandro Buschiazzo, Felipe Trajtenberg; Structural features of sensory two component systems: a synthetic biology perspective. Biochem J 31 January 2023; 480 (2): 127–140. doi: https://doi.org/10.1042/BCJ20210798
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