Transmembrane Signal Transduction in Two‐Component Systems: Piston, Scissoring, or Helical Rotation?

Gushchin, Ivan; Gordeliy, Valentin

doi:10.1002/bies.201700197

Cited by 51 publications

(88 citation statements)

References 132 publications

(254 reference statements)

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“…Owing to the periodicity of coiled coils, see above, within the SHK family these linkers are of discrete lengths and exhibit alternating hydrophilic and hydrophobic residues. 12,15,36,61,102 As recently summarized, 146 helical bundles can undergo a series of principal transitions including dissociation/association, rotation, supercoiling (or, twisting), piston, and pivot motions. As several of these transitions can mutually compensate another, they commonly occur in concert rather than isolation.…”

Section: The Dynamics Of α-Helical Coiled Coilsmentioning

confidence: 99%

Signal transduction in photoreceptor histidine kinases

Möglich

2019

Protein Science

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Two‐component systems (TCS) constitute the predominant means by which prokaryotes read out and adapt to their environment. Canonical TCSs comprise a sensor histidine kinase (SHK), usually a transmembrane receptor, and a response regulator (RR). In signal‐dependent manner, the SHK autophosphorylates and in turn transfers the phosphoryl group to the RR which then elicits downstream responses, often in form of altered gene expression. SHKs also catalyze the hydrolysis of the phospho‐RR, hence, tightly adjusting the overall degree of RR phosphorylation. Photoreceptor histidine kinases are a subset of mostly soluble, cytosolic SHKs that sense light in the near‐ultraviolet to near‐infrared spectral range. Owing to their experimental tractability, photoreceptor histidine kinases serve as paradigms and provide unusually detailed molecular insight into signal detection, decoding, and regulation of SHK activity. The synthesis of recent results on receptors with light‐oxygen‐voltage, bacteriophytochrome and microbial rhodopsin sensor units identifies recurring, joint signaling strategies. Light signals are initially absorbed by the sensor module and converted into subtle rearrangements of α helices, mostly through pivoting and rotation. These conformational transitions propagate through parallel coiled‐coil linkers to the effector unit as changes in left‐handed superhelical winding. Within the effector, subtle conformations are triggered that modulate the solvent accessibility of residues engaged in the kinase and phosphatase activities. Taken together, a consistent view of the entire trajectory from signal detection to regulation of output emerges. The underlying allosteric mechanisms could widely apply to TCS signaling in general.

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Section: The Dynamics Of α-Helical Coiled Coilsmentioning

confidence: 99%

Signal transduction in photoreceptor histidine kinases

Möglich

2019

Protein Science

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“…The ligand-binding site is located at the interface of two protomers (Milburn et al, 1991;Yeh et al, 1993), and ligands bind with a stoichiometry of one molecule per dimer (Milligan and Koshland, 1993). Ligandbinding initiates a piston-like downward sliding of the α4 helix within the integral chemoreceptors and the signal is further transmitted via piston and rotation movements of transmembrane helices generating conformational changes of the HAMP domains, and ultimately altering the CheA kinase activity (Chervitz and Falke, 1996;Ottemann et al, 1999;Hulko et al, 2006;Yu et al, 2015;Gushchin and Gordeliy, 2018).…”

Section: Introductionmentioning

confidence: 99%

The ligand‐binding domain of a chemoreceptor from Comamonas testosteroni has a previously unknown homotrimeric structure

Yuan

Huang

Guo

et al. 2019

Molecular Microbiology

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Summary Transmembrane chemoreceptors are widely present in Bacteria and Archaea. They play a critical role in sensing various signals outside and transmitting to the cell interior. Here, we report the structure of the periplasmic ligand‐binding domain (LBD) of the transmembrane chemoreceptor MCP2201, which governs chemotaxis to citrate and other organic compounds in Comamonas testosteroni. The apo‐form LBD crystal revealed a typical four‐helix bundle homodimer, similar to previously well‐studied chemoreceptors such as Tar and Tsr of Escherichia coli. However, the citrate‐bound LBD revealed a four‐helix bundle homotrimer that had not been observed in bacterial chemoreceptor LBDs. This homotrimer was further confirmed with size‐exclusion chromatography, analytical ultracentrifugation and cross‐linking experiments. The physiological importance of the homotrimer for chemotaxis was demonstrated with site‐directed mutations of key amino acid residues in C. testosteroni mutants.

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“…Aside from notable exceptions (10,11), HKs are canonically viewed as dimeric proteins with modular architecture that includes an extracytoplasmic sensor region, transmembrane (TM) helices, various signal transduction domains, and a kinase domain consisting of dimerization and histidine phosphotransfer (DHp) and catalytic ATP-binding (CA) subdomains (12,13). After the sensor detects its stimulus, the signal propagates through the TM and other intervening domains via a variety of motions alternatively described as piston-like motions, scissoring, or helical rotations (12), to the DHp helices. The CA domain then catalyzes the transfer of a phosphoryl group from the bound ATP substrate to the phosphoacceptor histidine located on the first DHp helix.…”

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confidence: 99%

Insights into histidine kinase activation mechanisms from the monomeric blue light sensor EL346

Dikiy

Edupuganti

Abzalimov

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Translation of environmental cues into cellular behavior is a necessary process in all forms of life. In bacteria, this process frequently involves two-component systems in which a sensor histidine kinase (HK) autophosphorylates in response to a stimulus before subsequently transferring the phosphoryl group to a response regulator that controls downstream effectors. Many details of the molecular mechanisms of HK activation are still unclear due to complications associated with the multiple signaling states of these large, multidomain proteins. To address these challenges, we combined complementary solution biophysical approaches to examine the conformational changes upon activation of a minimal, blue-light-sensing histidine kinase from Erythrobacter litoralis HTCC2594, EL346. Our data show that multiple conformations coexist in the dark state of EL346 in solution, which may explain the enzyme's residual dark-state activity. We also observe that activation involves destabilization of the helices in the dimerization and histidine phosphotransfer-like domain, where the phosphoacceptor histidine resides, and their interactions with the catalytic domain. Similar light-induced changes occur to some extent even in constitutively active or inactive mutants, showing that light sensing can be decoupled from activation of kinase activity. These structural changes mirror those inferred by comparing X-ray crystal structures of inactive and active HK fragments, suggesting that they are at the core of conformational changes leading to HK activation. More broadly, our findings uncover surprising complexity in this simple system and allow us to outline a mechanism of the multiple steps of HK activation.sensor histidine kinase | HDX-MS | ESR spectroscopy | two-component system | photoreceptor

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Transmembrane Signal Transduction in Two‐Component Systems: Piston, Scissoring, or Helical Rotation?

Cited by 51 publications

References 132 publications

Signal transduction in photoreceptor histidine kinases

Signal transduction in photoreceptor histidine kinases

The ligand‐binding domain of a chemoreceptor from Comamonas testosteroni has a previously unknown homotrimeric structure

Insights into histidine kinase activation mechanisms from the monomeric blue light sensor EL346

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