title: Phylogenetic distribution and membrane topology of the LytR-CpsA-Psr protein family.
abstract: BACKGROUND
  The bacterial cell wall is the target of many antibiotics and cell envelope constituents are critical to host-pathogen interactions. To combat resistance development and virulence, a detailed knowledge of the individual factors involved is essential. Members of the LytR-CpsA-Psr family of cell envelope-associated attenuators are relevant for beta-lactam resistance, biofilm formation, and stress tolerance, and they are suggested to play a role in cell wall maintenance. However, their precise function is still unknown. This study addresses the occurrence as well as sequence-based characteristics of the LytR-CpsA-Psr proteins.
  
  
  RESULTS
  A comprehensive list of LytR-CpsA-Psr proteins was established, and their phylogenetic distribution and clustering into subgroups was determined. LytR-CpsA-Psr proteins were present in all Gram-positive organisms, except for the cell wall-deficient Mollicutes and one strain of the Clostridiales. In contrast, the majority of Gram-negatives did not contain LytR-CpsA-Psr family members. Despite high sequence divergence, the LytR-CpsA-Psr domains of different subclusters shared a highly similar, predicted mixed a/beta-structure, and conserved charged residues. PhoA fusion experiments, using MsrR of Staphylococcus aureus, confirmed membrane topology predictions and extracellular location of its LytR-CpsA-Psr domain.
  
  
  CONCLUSIONS
  The LytR-CpsA-Psr domain is unique to bacteria. The presence of diverse subgroups within the LytR-CpsA-Psr family might indicate functional differences, and could explain variations in phenotypes of respective mutants reported. The identified conserved structural elements and amino acids are likely to be important for the function of the domain and will help to guide future studies of the LytR-CpsA-Psr proteins.
authors.affiliation: Institute of Medical Microbiology, University of Zürich, Zürich, Switzerland. jhuebsch@imm.uzh.ch
authors.forename: Judith
authors.initials: J
authors.lastname: Hübscher
authors.forename: Lucas
authors.initials: L
authors.lastname: Lüthy
authors.forename: Brigitte
authors.initials: B
authors.lastname: Berger-Bächi
authors.forename: Patricia
authors.initials: P
authors.lastname: Stutzmann Meier
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000145:classification* / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D017124:Conserved Sequence; D019143:Evolution, Molecular; D008565:Membrane Proteins / Q000737:chemistry* / Q000145:classification* / Q000235:genetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism; D008973:Tenericutes / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000145:classification* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D008565:Membrane Proteins; D014157:Transcription Factors