Abstract
Bacteria sense intracellular and environmental signals using an array of proteins as antennas. The information is transmitted from such sensory modules to other protein domains that act as output effectors. Sensor and effector can be part of the same polypeptide or instead be separate diffusible proteins that interact specifically. The output effector modules regulate physiologic responses, allowing the cells to adapt to the varying conditions. These biological machineries are known as signal transduction systems (STSs). Despite the captivating architectural diversity exhibited by STS proteins, a universal feature is their allosteric regulation: signal binding at one site modifies the activity at a physically distant site. Allostery requires protein plasticity, precisely encoded within their 3D structures, and implicating programmed molecular motions. This review summarizes how STS proteins connect stimuli to specific responses by exploiting allostery and protein plasticity. Illustrative examples spanning a wide variety of protein folds will focus on one- and two-component systems (TCSs). The former encompass the entire transmission route within a single polypeptide, whereas TCSs have evolved as separate diffusible proteins that interact specifically, sometimes including additional intermediary proteins in the pathway. Irrespective of their structural diversity, STS proteins are able to modulate their own molecular motions, which can be relatively slow, rigid-body movements, all the way to fast fluctuations in the form of macromolecular flexibility, thus spanning a continuous protein dynamics spectrum. In sum, STSs rely on allostery to steer information transmission, going from simple two-state switching to rich multi-state conformational order/disorder transitions.
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This study received funding from ANII (grant FCE_1_2017_1_136291) and from the Unit of Integrative Microbiology of Zoonotic Agents IMiZA, Joint International Units program, Institut Pasteur/Institut Pasteur de Montevideo.
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Imelio, J.A., Trajtenberg, F. & Buschiazzo, A. Allostery and protein plasticity: the keystones for bacterial signaling and regulation. Biophys Rev 13, 943–953 (2021). https://doi.org/10.1007/s12551-021-00892-9
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DOI: https://doi.org/10.1007/s12551-021-00892-9