Mechanism of sensor kinase CitA transmembrane signaling

Zhang XC, Xue K, Salvi M, Schomburg B, Mehrens J, Giller K, Stopp M, Weisenburger S, Böning D, Sandoghdar V, Unden G, Becker S, Andreas LB, Griesinger C (2025)

Publication Language: English

Publication Type: Journal article

Publication year: 2025

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 16

Article Number: 935

DOI: 10.1038/s41467-024-55671-3

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.

Authors with CRIS profile

Siegfried Weisenburger Lehrstuhl für Experimentalphysik Vahid Sandoghdar Lehrstuhl für Experimentalphysik

Involved external institutions

Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light DE Germany (DE) Max-Planck-Institut für Multidisziplinäre Naturwissenschaften / Max Planck Institute for Multidisciplinary Sciences DE Germany (DE) Johannes Gutenberg-Universität Mainz (JGU) DE Germany (DE)

How to cite

APA:

Zhang, X.C., Xue, K., Salvi, M., Schomburg, B., Mehrens, J., Giller, K.,... Griesinger, C. (2025). Mechanism of sensor kinase CitA transmembrane signaling. Nature Communications, 16. https://doi.org/10.1038/s41467-024-55671-3

MLA:

Zhang, Xizhou Cecily, et al. "Mechanism of sensor kinase CitA transmembrane signaling." Nature Communications 16 (2025).

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