Ligand-Induced Asymmetry in Histidine Sensor Kinase Complex Regulates Quorum Sensing

Matthew B. Neiditch; Michael J. Federle; Audra J. Pompeani; Robert C. Kelly; Danielle L. Swem; Philip D. Jeffrey; Bonnie L. Bassler; Frederick M. Hughson

doi:10.1016/j.cell.2006.07.032

Ligand-Induced Asymmetry in Histidine Sensor Kinase Complex Regulates Quorum Sensing

Matthew B. Neiditch, Michael J. Federle, Audra J. Pompeani, Robert C. Kelly, Danielle L. Swem, Philip D. Jeffrey, Bonnie L. Bassler, Frederick M. Hughson

Research output: Contribution to journal › Article › peer-review

235 Scopus citations

Abstract

Bacteria sense their environment using receptors of the histidine sensor kinase family, but how kinase activity is regulated by ligand binding is not well understood. Autoinducer-2 (AI-2), a secreted signaling molecule originally identified in studies of the marine bacterium Vibrio harveyi, regulates quorum-sensing responses and allows communication between different bacterial species. AI-2 signal transduction in V. harveyi requires the integral membrane receptor LuxPQ, comprised of periplasmic binding protein (LuxP) and histidine sensor kinase (LuxQ) subunits. Combined X-ray crystallographic and functional studies show that AI-2 binding causes a major conformational change within LuxP, which in turn stabilizes a quaternary arrangement in which two LuxPQ monomers are asymmetrically associated. We propose that formation of this asymmetric quaternary structure is responsible for repressing the kinase activity of both LuxQ subunits and triggering the transition of V. harveyi into quorum-sensing mode.

Original language	English (US)
Pages (from-to)	1095-1108
Number of pages	14
Journal	Cell
Volume	126
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2006.07.032
State	Published - Sep 22 2006

All Science Journal Classification (ASJC) codes

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2006.07.032

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@article{476e579a7cfe4927ac766b462f7d921b,

title = "Ligand-Induced Asymmetry in Histidine Sensor Kinase Complex Regulates Quorum Sensing",

abstract = "Bacteria sense their environment using receptors of the histidine sensor kinase family, but how kinase activity is regulated by ligand binding is not well understood. Autoinducer-2 (AI-2), a secreted signaling molecule originally identified in studies of the marine bacterium Vibrio harveyi, regulates quorum-sensing responses and allows communication between different bacterial species. AI-2 signal transduction in V. harveyi requires the integral membrane receptor LuxPQ, comprised of periplasmic binding protein (LuxP) and histidine sensor kinase (LuxQ) subunits. Combined X-ray crystallographic and functional studies show that AI-2 binding causes a major conformational change within LuxP, which in turn stabilizes a quaternary arrangement in which two LuxPQ monomers are asymmetrically associated. We propose that formation of this asymmetric quaternary structure is responsible for repressing the kinase activity of both LuxQ subunits and triggering the transition of V. harveyi into quorum-sensing mode.",

author = "Neiditch, {Matthew B.} and Federle, {Michael J.} and Pompeani, {Audra J.} and Kelly, {Robert C.} and Swem, {Danielle L.} and Jeffrey, {Philip D.} and Bassler, {Bonnie L.} and Hughson, {Frederick M.}",

note = "Funding Information: We gratefully acknowledge George DeTitta, Joseph Luft, and the staff of the High-Throughput Crystallization Laboratory of the Hauptman-Woodward Medical Research Institute for assistance in crystallization; Michael Becker and the staff of the National Synchrotron Light Source X25 beamline for assistance with X-ray data collection; Shawn Campagna and Martin Semmelhack for chemically synthesized DPD; Bashkim Kokona and Robert Fairman for equilibrium analytical ultracentrifugation; Yi Ren and Yufang Wang for additional experimental contributions; and Yigong Shi, Tom Silhavy, Ann Stock, Daniel Ungar, and Ned Wingreen for critical review of the manuscript and, together with members of our laboratories, for advice and discussion. This work was supported by NIH grants AI-054442 and GM-065859, HHMI, and NIH postdoctoral fellowships (to M.B.N. and M.J.F.). ",

year = "2006",

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doi = "10.1016/j.cell.2006.07.032",

language = "English (US)",

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T1 - Ligand-Induced Asymmetry in Histidine Sensor Kinase Complex Regulates Quorum Sensing

AU - Neiditch, Matthew B.

AU - Federle, Michael J.

AU - Pompeani, Audra J.

AU - Kelly, Robert C.

AU - Swem, Danielle L.

AU - Jeffrey, Philip D.

AU - Bassler, Bonnie L.

AU - Hughson, Frederick M.

N1 - Funding Information: We gratefully acknowledge George DeTitta, Joseph Luft, and the staff of the High-Throughput Crystallization Laboratory of the Hauptman-Woodward Medical Research Institute for assistance in crystallization; Michael Becker and the staff of the National Synchrotron Light Source X25 beamline for assistance with X-ray data collection; Shawn Campagna and Martin Semmelhack for chemically synthesized DPD; Bashkim Kokona and Robert Fairman for equilibrium analytical ultracentrifugation; Yi Ren and Yufang Wang for additional experimental contributions; and Yigong Shi, Tom Silhavy, Ann Stock, Daniel Ungar, and Ned Wingreen for critical review of the manuscript and, together with members of our laboratories, for advice and discussion. This work was supported by NIH grants AI-054442 and GM-065859, HHMI, and NIH postdoctoral fellowships (to M.B.N. and M.J.F.).

PY - 2006/9/22

Y1 - 2006/9/22

N2 - Bacteria sense their environment using receptors of the histidine sensor kinase family, but how kinase activity is regulated by ligand binding is not well understood. Autoinducer-2 (AI-2), a secreted signaling molecule originally identified in studies of the marine bacterium Vibrio harveyi, regulates quorum-sensing responses and allows communication between different bacterial species. AI-2 signal transduction in V. harveyi requires the integral membrane receptor LuxPQ, comprised of periplasmic binding protein (LuxP) and histidine sensor kinase (LuxQ) subunits. Combined X-ray crystallographic and functional studies show that AI-2 binding causes a major conformational change within LuxP, which in turn stabilizes a quaternary arrangement in which two LuxPQ monomers are asymmetrically associated. We propose that formation of this asymmetric quaternary structure is responsible for repressing the kinase activity of both LuxQ subunits and triggering the transition of V. harveyi into quorum-sensing mode.

AB - Bacteria sense their environment using receptors of the histidine sensor kinase family, but how kinase activity is regulated by ligand binding is not well understood. Autoinducer-2 (AI-2), a secreted signaling molecule originally identified in studies of the marine bacterium Vibrio harveyi, regulates quorum-sensing responses and allows communication between different bacterial species. AI-2 signal transduction in V. harveyi requires the integral membrane receptor LuxPQ, comprised of periplasmic binding protein (LuxP) and histidine sensor kinase (LuxQ) subunits. Combined X-ray crystallographic and functional studies show that AI-2 binding causes a major conformational change within LuxP, which in turn stabilizes a quaternary arrangement in which two LuxPQ monomers are asymmetrically associated. We propose that formation of this asymmetric quaternary structure is responsible for repressing the kinase activity of both LuxQ subunits and triggering the transition of V. harveyi into quorum-sensing mode.

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JO - Cell

JF - Cell

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ER -

Ligand-Induced Asymmetry in Histidine Sensor Kinase Complex Regulates Quorum Sensing

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