TY - JOUR
T1 - Sensor domain of histidine kinase VxrA of vibrio cholerae
T2 - hairpin-swapped dimer and its conformational change
AU - Tan, Kemin
AU - Teschler, Jennifer K.
AU - Wu, Ruiying
AU - Jedrzejczak, Robert P.
AU - Zhou, Min
AU - Shuvalova, Ludmilla A.
AU - Endres, Michael J.
AU - Welk, Lucas F.
AU - Kwon, Keehwan
AU - Anderson, Wayne F.
AU - Satchell, Karla J.F.
AU - Yildiz, Fitnat H.
AU - Joachimiak, Andrzej
N1 - Funding Information:
This work was supported by federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Department of Health and Human Services, under contract numbers HHSN272201200026C (to W.F.A.) and HHSN272201700060C (to K.J.F.S.) and the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) grant R01AI055987 to F.H.Y. The Structural Biology Center beamlines are supported by U.S. Department of Energy, Office of Biological and Environmental Research, under contract DE-AC02-06CH11357. The submitted paper was created by UChicago Argonne, LLC, Operator of Argonne National Laboratory (Argonne). Argonne, a U.S. Department of Energy Office of Science laboratory, is operated under contract number DE-AC02-06CH11357.
Publisher Copyright:
Copyright © 2021 American Society for Microbiology. All Rights Reserved.
PY - 2021/6
Y1 - 2021/6
N2 - VxrA and VxrB are cognate histidine kinase (HK)-response regulator (RR) pairs of a two-component signaling system (TCS) found in Vibrio cholerae, a bacterial pathogen that causes cholera. The VxrAB TCS positively regulates virulence, the type VI secretion system, biofilm formation, and cell wall homeostasis in V. cholerae, providing protection from environmental stresses and contributing to the transmission and virulence of the pathogen. The VxrA HK has a unique periplasmic sensor domain (SD) and, remarkably, lacks a cytoplasmic linker domain between the second transmembrane helix and the dimerization and histidine phosphotransfer (DHp) domain, indicating that this system may utilize a potentially unique signal sensing and transmission TCS mechanism. In this study, we have determined several crystal structures of VxrA-SD and its mutants. These structures reveal a novel structural fold forming an unusual b hairpin-swapped dimer. A conformational change caused by relative rotation of the two monomers in a VxrA-SD dimer could potentially change the association of transmembrane helices and, subsequently, the pairing of cytoplasmic DHp domains. Based on the structural observation, we propose a putative scissor-like closing regulation mechanism for the VxrA HK. IMPORTANCE V. cholerae has a dynamic life cycle, which requires rapid adaptation to changing external conditions. Two-component signal transduction (TCS) systems allow V. cholerae to sense and respond to these environmental changes. The VxrAB TCS positively regulates a number of important V. cholerae phenotypes, including virulence, the type six secretion system, biofilm formation, and cell wall homeostasis. Here, we provide the crystal structures of the VxrA sensor histidine kinase sensing domain and propose a mechanism for signal transduction. The cognate signal for VxrAB remains unknown; however, in this work we couple our structural analysis with functional assessments of key residues to further our understanding of this important TCS.
AB - VxrA and VxrB are cognate histidine kinase (HK)-response regulator (RR) pairs of a two-component signaling system (TCS) found in Vibrio cholerae, a bacterial pathogen that causes cholera. The VxrAB TCS positively regulates virulence, the type VI secretion system, biofilm formation, and cell wall homeostasis in V. cholerae, providing protection from environmental stresses and contributing to the transmission and virulence of the pathogen. The VxrA HK has a unique periplasmic sensor domain (SD) and, remarkably, lacks a cytoplasmic linker domain between the second transmembrane helix and the dimerization and histidine phosphotransfer (DHp) domain, indicating that this system may utilize a potentially unique signal sensing and transmission TCS mechanism. In this study, we have determined several crystal structures of VxrA-SD and its mutants. These structures reveal a novel structural fold forming an unusual b hairpin-swapped dimer. A conformational change caused by relative rotation of the two monomers in a VxrA-SD dimer could potentially change the association of transmembrane helices and, subsequently, the pairing of cytoplasmic DHp domains. Based on the structural observation, we propose a putative scissor-like closing regulation mechanism for the VxrA HK. IMPORTANCE V. cholerae has a dynamic life cycle, which requires rapid adaptation to changing external conditions. Two-component signal transduction (TCS) systems allow V. cholerae to sense and respond to these environmental changes. The VxrAB TCS positively regulates a number of important V. cholerae phenotypes, including virulence, the type six secretion system, biofilm formation, and cell wall homeostasis. Here, we provide the crystal structures of the VxrA sensor histidine kinase sensing domain and propose a mechanism for signal transduction. The cognate signal for VxrAB remains unknown; however, in this work we couple our structural analysis with functional assessments of key residues to further our understanding of this important TCS.
KW - Conformational change
KW - Dimerization
KW - Mutagenesis
KW - Sensor domain
KW - Signal transduction
KW - Two-component system
KW - Vibrio cholerae
KW - VxrA histidine kinase
KW - VxrAB
KW - X-ray crystallography
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U2 - 10.1128/JB.00643-20
DO - 10.1128/JB.00643-20
M3 - Article
C2 - 33753465
AN - SCOPUS:85105848498
VL - 203
JO - Journal of Bacteriology
JF - Journal of Bacteriology
SN - 0021-9193
IS - 11
M1 - e00643
ER -
