Sensor Domain of Histidine Kinase VxrA of Vibrio cholerae: Hairpin-Swapped Dimer and Its Conformational Change

Tan, Kemin; Teschler, Jennifer K.; Wu, Ruiying; Jedrzejczak, Robert P.; Zhou, Min; Shuvalova, Ludmilla A.; Endres, Michael J.; Welk, Lucas F.; Kwon, Keehwan; Anderson, Wayne F.; Satchell, Karla F.; Yildiz, Fitnat H.; Joachimiak, Andrzej

doi:10.1128/jb.00643-20

Sensor Domain of Histidine Kinase VxrA of Vibrio cholerae: Hairpin-Swapped Dimer and Its Conformational Change

Journal Article · Fri May 07 00:00:00 EDT 2021 · Journal of Bacteriology

DOI:https://doi.org/10.1128/jb.00643-20· OSTI ID:1798317

^[1]; Teschler, Jennifer K. ^[2]; Wu, Ruiying ^[3]; Jedrzejczak, Robert P. ^[3]; Zhou, Min ^[4]; Shuvalova, Ludmilla A. ^[5]; Endres, Michael J. ^[3]; Welk, Lucas F. ^[4]; Kwon, Keehwan ^[6]; Anderson, Wayne F. ^[5]; ^[7]; ^[2]; ^[1]

Univ. of Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)
Univ. of California, Santa Cruz, CA (United States)
Univ. of Chicago, IL (United States)
Argonne National Lab. (ANL), Argonne, IL (United States)
Northwestern Univ., Evanston, IL (United States)
Northwestern Univ., Evanston, IL (United States); J. Craig Venter Inst., Rockville, MD (United States); GSK, Collegeville, PA (United States)
Center for Structural Genomics of Infectious Diseases, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

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. Here, we have determined several crystal structures of VxrA-SD and its mutants. These structures reveal a novel structural fold forming an unusual β 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.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1798317

Journal Information:: Journal of Bacteriology, Journal Name: Journal of Bacteriology Journal Issue: 11 Vol. 203; ISSN 0021-9193

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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dimerization
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Sensor Domain of Histidine Kinase VxrA of Vibrio cholerae: Hairpin-Swapped Dimer and Its Conformational Change

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