Mechanism of sensor kinase CitA transmembrane signaling
Abstract Membrane bound histidine kinases (HKs) are ubiquitous sensors of extracellular stimuli in bacteria. However, a uniform structural model is still missing for their transmembrane signaling mechanism. Here, we used solid-state NMR in conjunction with crystallography, solution NMR and distance...
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| Format: | Article |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55671-3 |
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| author | Xizhou Cecily Zhang Kai Xue Michele Salvi Benjamin Schomburg Jonas Mehrens Karin Giller Marius Stopp Siegfried Weisenburger Daniel Böning Vahid Sandoghdar Gottfried Unden Stefan Becker Loren B. Andreas Christian Griesinger |
| author_facet | Xizhou Cecily Zhang Kai Xue Michele Salvi Benjamin Schomburg Jonas Mehrens Karin Giller Marius Stopp Siegfried Weisenburger Daniel Böning Vahid Sandoghdar Gottfried Unden Stefan Becker Loren B. Andreas Christian Griesinger |
| author_sort | Xizhou Cecily Zhang |
| collection | DOAJ |
| description | Abstract Membrane bound histidine kinases (HKs) are ubiquitous sensors of extracellular stimuli in bacteria. However, a uniform structural model is still missing for their transmembrane signaling mechanism. Here, we used solid-state NMR in conjunction with crystallography, solution NMR and distance measurements to investigate the transmembrane signaling mechanism of a paradigmatic citrate sensing membrane embedded HK, CitA. Citrate binding in the sensory extracytoplasmic PAS domain (PASp) causes the linker to transmembrane helix 2 (TM2) to adopt a helical conformation. This triggers a piston-like pulling of TM2 and a quaternary structure rearrangement in the cytosolic PAS domain (PASc). Crystal structures of PASc reveal both anti-parallel and parallel dimer conformations. An anti-parallel to parallel transition upon citrate binding agrees with interdimer distances measured in the lipid embedded protein using a site-specific 19F label in PASc. These data show how Angstrom scale structural changes in the sensor domain are transmitted across the membrane to be converted and amplified into a nm scale shift in the linker to the phosphorylation subdomain of the kinase. |
| format | Article |
| id | doaj-art-6d5a6bc4743b46c2baa5ffdd20fe3cd4 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-6d5a6bc4743b46c2baa5ffdd20fe3cd42025-01-26T12:41:25ZengNature PortfolioNature Communications2041-17232025-01-0116111110.1038/s41467-024-55671-3Mechanism of sensor kinase CitA transmembrane signalingXizhou Cecily Zhang0Kai Xue1Michele Salvi2Benjamin Schomburg3Jonas Mehrens4Karin Giller5Marius Stopp6Siegfried Weisenburger7Daniel Böning8Vahid Sandoghdar9Gottfried Unden10Stefan Becker11Loren B. Andreas12Christian Griesinger13NMR-based Structural Biology, Max Planck Institute for Multidisciplinary SciencesNMR-based Structural Biology, Max Planck Institute for Multidisciplinary SciencesNMR-based Structural Biology, Max Planck Institute for Multidisciplinary SciencesNMR-based Structural Biology, Max Planck Institute for Multidisciplinary SciencesNMR-based Structural Biology, Max Planck Institute for Multidisciplinary SciencesNMR-based Structural Biology, Max Planck Institute for Multidisciplinary SciencesInstitute for Molecular Physiology (imP), Microbiology and Biotechnology, Johannes Gutenberg UniversityDepartment of Physics, Friedrich Alexander University (FAU) Erlangen-NürnbergDepartment of Physics, Friedrich Alexander University (FAU) Erlangen-NürnbergDepartment of Physics, Friedrich Alexander University (FAU) Erlangen-NürnbergInstitute for Molecular Physiology (imP), Microbiology and Biotechnology, Johannes Gutenberg UniversityNMR-based Structural Biology, Max Planck Institute for Multidisciplinary SciencesNMR-based Structural Biology, Max Planck Institute for Multidisciplinary SciencesNMR-based Structural Biology, Max Planck Institute for Multidisciplinary SciencesAbstract Membrane bound histidine kinases (HKs) are ubiquitous sensors of extracellular stimuli in bacteria. However, a uniform structural model is still missing for their transmembrane signaling mechanism. Here, we used solid-state NMR in conjunction with crystallography, solution NMR and distance measurements to investigate the transmembrane signaling mechanism of a paradigmatic citrate sensing membrane embedded HK, CitA. Citrate binding in the sensory extracytoplasmic PAS domain (PASp) causes the linker to transmembrane helix 2 (TM2) to adopt a helical conformation. This triggers a piston-like pulling of TM2 and a quaternary structure rearrangement in the cytosolic PAS domain (PASc). Crystal structures of PASc reveal both anti-parallel and parallel dimer conformations. An anti-parallel to parallel transition upon citrate binding agrees with interdimer distances measured in the lipid embedded protein using a site-specific 19F label in PASc. These data show how Angstrom scale structural changes in the sensor domain are transmitted across the membrane to be converted and amplified into a nm scale shift in the linker to the phosphorylation subdomain of the kinase.https://doi.org/10.1038/s41467-024-55671-3 |
| spellingShingle | Xizhou Cecily Zhang Kai Xue Michele Salvi Benjamin Schomburg Jonas Mehrens Karin Giller Marius Stopp Siegfried Weisenburger Daniel Böning Vahid Sandoghdar Gottfried Unden Stefan Becker Loren B. Andreas Christian Griesinger Mechanism of sensor kinase CitA transmembrane signaling Nature Communications |
| title | Mechanism of sensor kinase CitA transmembrane signaling |
| title_full | Mechanism of sensor kinase CitA transmembrane signaling |
| title_fullStr | Mechanism of sensor kinase CitA transmembrane signaling |
| title_full_unstemmed | Mechanism of sensor kinase CitA transmembrane signaling |
| title_short | Mechanism of sensor kinase CitA transmembrane signaling |
| title_sort | mechanism of sensor kinase cita transmembrane signaling |
| url | https://doi.org/10.1038/s41467-024-55671-3 |
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