7CJR

Crystal structure of a periplasmic sensor domain of histidine kinase VbrK

Summary for 7CJR

• Entry DOI: 10.2210/pdb7cjr/pdb
• Descriptor: Histidine kinase, CHLORIDE ION, DI(HYDROXYETHYL)ETHER, ... (4 entities in total)
• Functional Keywords: histidine kinase, sensor, signaling protein, transferase, tetratricopeptide repeat
• Biological source: Vibrio parahaemolyticus
• Total number of polymer chains: 1
• Total formula weight: 27636.93

Authors

Goh, B.C.,Chua, Y.K.,Qian, X.,Savko, M.,Lescar, J. (deposition date: 2020-07-12, release date: 2020-09-16, Last modification date: 2024-11-13)

Primary citation

Goh, B.C.,Chua, Y.K.,Qian, X.,Lin, J.,Savko, M.,Dedon, P.C.,Lescar, J.
Crystal structure of the periplasmic sensor domain of histidine kinase VbrK suggests indirect sensing of beta-lactam antibiotics.
J.Struct.Biol., 212:107610-107610, 2020

PubMed Abstract: Bacterial two-component regulatory systems (TCS) play important roles in sensing environmental stimuli and responding to them by regulating gene expression. VbrK/VbrR, a TCS in Vibrio parahaemolyticus, confers resistance to β-lactam antibiotics through activating a β-lactamase gene. Its periplasmic sensor domain was previously suggested to detect β-lactam antibiotics by direct binding. Here, we report a crystal structure of the periplasmic sensing domain of VbrK (VbrK) using sulfur-based single-wavelength anomalous diffraction (S-SAD) phasing. Contrary to most bacterial sensor domains which form dimers, we show that VbrK is a monomer using size exclusion chromatography coupled with multi-angle light scattering. This observation is also supported by molecular dynamics simulations. To quantify the binding affinity of β-lactam antibiotics to VbrK, we performed isothermal titration calorimetry and other biophysical analyses. Unexpectedly, VbrK did not show any significant binding to β-lactam antibiotics. Therefore, we propose that the detection of β-lactam antibiotics by VbrK is likely to be indirect via an as yet unidentified mechanism.

PubMed: 32890780
DOI: 10.1016/j.jsb.2020.107610

Experimental method

X-RAY DIFFRACTION (2.28 Å)