title: Regulation of LuxPQ receptor activity by the quorum-sensing signal autoinducer-2.
abstract: The extracellular signaling molecule autoinducer-2 (AI-2) mediates quorum-sensing communication in diverse bacterial species. In marine vibrios, binding of AI-2 to the periplasmic receptor LuxP modulates the activity of the inner membrane sensor kinase LuxQ, transducing the AI-2 information into the cytoplasm. Here, we show that Vibrio harveyi LuxP associates with LuxQ in both the presence and absence of AI-2. The 1.9 A X-ray crystal structure of apoLuxP, complexed with the periplasmic domain of LuxQ, reveals that the latter contains two tandem Per/ARNT/Simple-minded (PAS) folds. Thus, although many prokaryotic PAS folds themselves bind ligands, the LuxQ periplasmic PAS folds instead bind LuxP, monitoring its AI-2 occupancy. Mutations that disrupt the apoLuxP:LuxQ interface sensitize V. harveyi to AI-2, implying that AI-2 binding causes the replacement of one set of LuxP:LuxQ contacts with another. These conformational changes switch LuxQ between two opposing enzymatic activities, each of which conveys information to the cytoplasm about the cell density of the surrounding environment.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Neiditch
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Federle
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Miller
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Bassler
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hughson
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006714:Homoserine / Q000031:analogs & derivatives* / Q000378:metabolism*; D007783:Lactones / Q000378:metabolism*; D008164:Luminescent Proteins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D010770:Phosphotransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014733:Vibrio / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D007783:Lactones; D008164:Luminescent Proteins; C090749:LuxP protein, Vibrio; D046912:Multiprotein Complexes; C091088:N-octanoylhomoserine lactone; D014157:Transcription Factors; D006714:Homoserine; D010770:Phosphotransferases; C090750:luxQ protein, Vibrio harveyi