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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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
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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| Summary: | 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. |
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| ISSN: | 2041-1723 |