Sensor Histidine Kinase NarQ Activates via Helical Rotation, Diagonal Scissoring, and Eventually Piston-Like Shifts
Membrane-embedded sensor histidine kinases (HKs) and chemoreceptors are used ubiquitously by bacteria and archaea to percept the environment, and are often crucial for their survival and pathogenicity. The proteins can transmit the signal from the sensor domain to the catalytic kinase domain reliabl...
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MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
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| author | Ivan Gushchin Philipp Orekhov Igor Melnikov Vitaly Polovinkin Anastasia Yuzhakova Valentin Gordeliy |
| author_facet | Ivan Gushchin Philipp Orekhov Igor Melnikov Vitaly Polovinkin Anastasia Yuzhakova Valentin Gordeliy |
| author_sort | Ivan Gushchin |
| collection | DOAJ |
| description | Membrane-embedded sensor histidine kinases (HKs) and chemoreceptors are used ubiquitously by bacteria and archaea to percept the environment, and are often crucial for their survival and pathogenicity. The proteins can transmit the signal from the sensor domain to the catalytic kinase domain reliably over the span of several hundreds of angstroms, and regulate the activity of the cognate response regulator proteins, with which they form two-component signaling systems (TCSs). Several mechanisms of transmembrane signal transduction in TCS receptors have been proposed, dubbed (swinging) piston, helical rotation, and diagonal scissoring. Yet, despite decades of studies, there is no consensus on whether these mechanisms are common for all TCS receptors. Here, we extend our previous work on <i>Escherichia coli</i> nitrate/nitrite sensor kinase NarQ. We determined a crystallographic structure of the sensor-TM-HAMP fragment of the R50S mutant, which, unexpectedly, was found in a ligand-bound-like conformation, despite an inability to bind nitrate. Subsequently, we reanalyzed the structures of the ligand-free and ligand-bound NarQ and NarX sensor domains, and conducted extensive molecular dynamics simulations of ligand-free and ligand-bound wild type and mutated NarQ. Based on the data, we show that binding of nitrate to NarQ causes, first and foremost, helical rotation and diagonal scissoring of the α-helices at the core of the sensor domain. These conformational changes are accompanied by a subtle piston-like motion, which is amplified by a switch in the secondary structure of the linker between the sensor and TM domains. We conclude that helical rotation, diagonal scissoring, and piston are simply different degrees of freedom in coiled-coil proteins and are not mutually exclusive in NarQ, and likely in other nitrate sensors and TCS proteins as well. |
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| last_indexed | 2024-03-10T20:10:47Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bff2b31de11c4e2bb4ed151e945611e72023-11-19T22:57:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01219311010.3390/ijms21093110Sensor Histidine Kinase NarQ Activates via Helical Rotation, Diagonal Scissoring, and Eventually Piston-Like ShiftsIvan Gushchin0Philipp Orekhov1Igor Melnikov2Vitaly Polovinkin3Anastasia Yuzhakova4Valentin Gordeliy5Research Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, RussiaResearch Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, RussiaInstitute of Biological Information Processing (IBI-7: Structural Biochemistry), Forschungszentrum Jülich, 52428 Jülich, GermanyResearch Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, RussiaResearch Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, RussiaResearch Center for Molecular Mechanisms of Aging and Age-Related Diseases, Moscow Institute of Physics and Technology, 141700 Dolgoprudny, RussiaMembrane-embedded sensor histidine kinases (HKs) and chemoreceptors are used ubiquitously by bacteria and archaea to percept the environment, and are often crucial for their survival and pathogenicity. The proteins can transmit the signal from the sensor domain to the catalytic kinase domain reliably over the span of several hundreds of angstroms, and regulate the activity of the cognate response regulator proteins, with which they form two-component signaling systems (TCSs). Several mechanisms of transmembrane signal transduction in TCS receptors have been proposed, dubbed (swinging) piston, helical rotation, and diagonal scissoring. Yet, despite decades of studies, there is no consensus on whether these mechanisms are common for all TCS receptors. Here, we extend our previous work on <i>Escherichia coli</i> nitrate/nitrite sensor kinase NarQ. We determined a crystallographic structure of the sensor-TM-HAMP fragment of the R50S mutant, which, unexpectedly, was found in a ligand-bound-like conformation, despite an inability to bind nitrate. Subsequently, we reanalyzed the structures of the ligand-free and ligand-bound NarQ and NarX sensor domains, and conducted extensive molecular dynamics simulations of ligand-free and ligand-bound wild type and mutated NarQ. Based on the data, we show that binding of nitrate to NarQ causes, first and foremost, helical rotation and diagonal scissoring of the α-helices at the core of the sensor domain. These conformational changes are accompanied by a subtle piston-like motion, which is amplified by a switch in the secondary structure of the linker between the sensor and TM domains. We conclude that helical rotation, diagonal scissoring, and piston are simply different degrees of freedom in coiled-coil proteins and are not mutually exclusive in NarQ, and likely in other nitrate sensors and TCS proteins as well.https://www.mdpi.com/1422-0067/21/9/3110two-component systemshistidine kinasereceptortransmembrane signalingX-ray crystallographymolecular dynamics |
| spellingShingle | Ivan Gushchin Philipp Orekhov Igor Melnikov Vitaly Polovinkin Anastasia Yuzhakova Valentin Gordeliy Sensor Histidine Kinase NarQ Activates via Helical Rotation, Diagonal Scissoring, and Eventually Piston-Like Shifts International Journal of Molecular Sciences two-component systems histidine kinase receptor transmembrane signaling X-ray crystallography molecular dynamics |
| title | Sensor Histidine Kinase NarQ Activates via Helical Rotation, Diagonal Scissoring, and Eventually Piston-Like Shifts |
| title_full | Sensor Histidine Kinase NarQ Activates via Helical Rotation, Diagonal Scissoring, and Eventually Piston-Like Shifts |
| title_fullStr | Sensor Histidine Kinase NarQ Activates via Helical Rotation, Diagonal Scissoring, and Eventually Piston-Like Shifts |
| title_full_unstemmed | Sensor Histidine Kinase NarQ Activates via Helical Rotation, Diagonal Scissoring, and Eventually Piston-Like Shifts |
| title_short | Sensor Histidine Kinase NarQ Activates via Helical Rotation, Diagonal Scissoring, and Eventually Piston-Like Shifts |
| title_sort | sensor histidine kinase narq activates via helical rotation diagonal scissoring and eventually piston like shifts |
| topic | two-component systems histidine kinase receptor transmembrane signaling X-ray crystallography molecular dynamics |
| url | https://www.mdpi.com/1422-0067/21/9/3110 |
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