Structure of the Escherichia coli quorum sensing protein SdiA: activation of the folding switch by acyl homoserine lactones.
The three-dimensional structure of a complex between the N-terminal domain of the quorum sensing protein SdiA of Escherichia coli and a candidate autoinducer N-octanoyl-L-homoserine lactone (C8-HSL) has been calculated in solution from NMR data. The SdiA-HSL system shows the "folding switch" behavior that has been seen for quorum-sensing factors produced by other bacterial species. In the presence of C8-HSL, a significant proportion of the SdiA protein is produced in a folded, soluble form in an E.coli expression system, whereas in the absence of acyl homoserine lactones, the protein is expressed into insoluble inclusion bodies. In the three-dimensional structure, the autoinducer molecule is sequestered in a deep pocket in the hydrophobic core, forming an integral part of the core packing of the folded SdiA. The NMR spectra of the complex show that the bound C8-HSL is conformationally heterogeneous, either due to motion within the pocket or to heterogeneity of the bound structure. The C8-HSL conformation is defined by NOEs to the protein only at the terminal methyl group of the octanoyl chain. Unlike other well-studied bacterial quorum sensing systems such as LuxR of Vibrio fischeri and TraR of Agrobacterium tumefaciens, there is no endogenous autoinducer for SdiA in E.coli: the E.coli genome does not contain a gene analogous to the LuxI and TraI autoinducer synthetases. We show that two other homoserine lactone derivatives are also capable of acting as a folding-switch autoinducers for SdiA. The observed structural heterogeneity of the bound C8-HSL in the complex, together with the variety of autoinducer-type molecules that can apparently act as folding switches in this system, are consistent with the postulated biological function of the SdiA protein as a detector of the presence of other species of bacteria.
Yao
Yong
Y
Department of Molecular Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Martinez-Yamout
Maria A
MA
Dickerson
Tobin J
TJ
Brogan
Andrew P
AP
Wright
Peter E
PE
Dyson
H Jane
HJ
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000187:drug effects; D006714:Homoserine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D012996:Solutions / Q000737:chemistry; D040681:Structural Homology, Protein; D015534:Trans-Activators / Q000737:chemistry* / Q000187:drug effects
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D007783:Lactones; C091088:N-octanoylhomoserine lactone; D012996:Solutions; C080512:TraR protein, Agrobacterium tumefaciens; D015534:Trans-Activators; C490806:sdiA protein, E coli; D006714:Homoserine