Bile salt receptor complex activates a pathogenic type III secretion system

Li, Peng; Rivera-Cancel, Giomar; Kinch, Lisa N.; Salomon, Dor; Tomchick, Diana R.; Grishin, Nick V.; Orth, Kim

doi:10.7554/eLife.15718

Title: Bile salt receptor complex activates a pathogenic type III secretion system

Journal Article · Tue Jul 05 00:00:00 EDT 2016 · eLife

DOI:https://doi.org/10.7554/eLife.15718· OSTI ID:1260282

Li, Peng ^[1]; Rivera-Cancel, Giomar ^[1]; Kinch, Lisa N. ^[2]; Salomon, Dor ^[1];

^[3]; Grishin, Nick V. ^[4];

^[5]

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States, Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States, Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, United States
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, United States, Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, United States

Bile is an important component of the human gastrointestinal tract with an essential role in food absorption and antimicrobial activities. Enteric bacterial pathogens have developed strategies to sense bile as an environmental cue to regulate virulence genes during infection. We discovered that Vibrio parahaemolyticus VtrC, along with VtrA and VtrB, are required for activating the virulence type III secretion system 2 in response to bile salts. The VtrA/VtrC complex activates VtrB in the presence of bile salts. The crystal structure of the periplasmic domains of the VtrA/VtrC heterodimer reveals a β-barrel with a hydrophobic inner chamber. A co-crystal structure of VtrA/VtrC with bile salt, along with biophysical and mutational analysis, demonstrates that the hydrophobic chamber binds bile salts and activates the virulence network. As part of a family of conserved signaling receptors, VtrA/VtrC provides structural and functional insights into the evolutionarily conserved mechanism used by bacteria to sense their environment.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1260282

Alternate ID(s):: OSTI ID: 1260283

Journal Information:: eLife, Journal Name: eLife Vol. 5; ISSN 2050-084X

Publisher:: eLife Sciences Publications, Ltd.Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 50 works

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