A structural genomics approach to the study of quorum sensing: crystal structures of three LuxS orthologs

Structure. 2001 Jun;9(6):527-37. doi: 10.1016/s0969-2126(01)00613-x.

Abstract

Background: Quorum sensing is the mechanism by which bacteria control gene expression in response to cell density. Two major quorum-sensing systems have been identified, system 1 and system 2, each with a characteristic signaling molecule (autoinducer-1, or AI-1, in the case of system 1, and AI-2 in system 2). The luxS gene is required for the AI-2 system of quorum sensing. LuxS and AI-2 have been described in both Gram-negative and Gram-positive bacterial species and have been shown to be involved in the expression of virulence genes in several pathogens.

Results: The structure of the LuxS protein from three different bacterial species with resolutions ranging from 1.8 A to 2.4 A has been solved using an X-ray crystallographic structural genomics approach. The structure of LuxS reported here is seen to have a new alpha-beta fold. In all structures, an equivalent homodimer is observed. A metal ion identified as zinc was seen bound to a Cys-His-His triad. Methionine was found bound to the protein near the metal and at the dimer interface.

Conclusions: These structures provide support for a hypothesis that explains the in vivo action of LuxS. Specifically, acting as a homodimer, the protein binds a methionine analog, S-ribosylhomocysteine (SRH). The zinc atom is in position to cleave the ribose ring in a step along the synthesis pathway of AI-2.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Binding Sites
  • Carbon-Sulfur Lyases
  • Crystallography, X-Ray
  • Dimerization
  • Genome, Bacterial*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Sequence Homology, Amino Acid

Substances

  • Bacterial Proteins
  • Carbon-Sulfur Lyases
  • LuxS protein, Bacteria

Associated data

  • PDB/1INN
  • PDB/1J6V
  • PDB/1J6W
  • PDB/1J6X