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Crystal structure of a periplasmic sensor domain of histidine kinase VbrKCrystal structure of a periplasmic sensor domain of histidine kinase VbrK
Structural highlights
Publication Abstract from PubMedBacterial 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 beta-lactam antibiotics through activating a beta-lactamase gene. Its periplasmic sensor domain was previously suggested to detect beta-lactam antibiotics by direct binding. Here, we report a crystal structure of the periplasmic sensing domain of VbrK (VbrK(SD)) using sulfur-based single-wavelength anomalous diffraction (S-SAD) phasing. Contrary to most bacterial sensor domains which form dimers, we show that VbrK(SD) 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 beta-lactam antibiotics to VbrK(SD), we performed isothermal titration calorimetry and other biophysical analyses. Unexpectedly, VbrK(SD) did not show any significant binding to beta-lactam antibiotics. Therefore, we propose that the detection of beta-lactam antibiotics by VbrK is likely to be indirect via an as yet unidentified mechanism. Crystal structure of the periplasmic sensor domain of histidine kinase VbrK suggests indirect sensing of beta-lactam antibiotics.,Goh BC, Chua YK, Qian X, Lin J, Savko M, Dedon PC, Lescar J J Struct Biol. 2020 Sep 2;212(2):107610. doi: 10.1016/j.jsb.2020.107610. PMID:32890780[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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