A processive lipid glycosyltransferase in the small human pathogen Mycoplasma pneumoniae: involvement in host immune response

Mol Microbiol. 2007 Sep;65(6):1444-57. doi: 10.1111/j.1365-2958.2007.05865.x. Epub 2007 Aug 14.

Abstract

The human pathogen Mycoplasma pneumoniae has a very small genome but with many yet not identified gene functions, e.g. for membrane lipid biosynthesis. Extensive radioactive labelling in vivo and enzyme assays in vitro revealed a substantial capacity for membrane glycolipid biosynthesis, yielding three glycolipids, five phosphoglycolipids, in addition to six phospholipids. Most glycolipids were synthesized in a cell protein/lipid-detergent extract in vitro; galactose was incorporated into all species, whereas glucose only into a few. One (MPN483) of the three predicted glycosyltransferases (GTs; all essential) was both processive and promiscuous, synthesizing most of the identified glycolipids. These enzymes are of a GT-A fold, similar to an established structure, and belong to CAZy GT-family 2. The cloned MPN483 could use both diacylglycerol (DAG) and human ceramide acceptor substrates, and in particular UDP-galactose but also UDP-glucose as donors, making mono-, di- and trihexose variants. MPN483 output and processitivity was strongly influenced by the local lipid environment of anionic lipids. The structure of a major beta1,6GlcbetaGalDAG species was determined by NMR spectroscopy. This, as well as other purified M. pneumoniae glycolipid species, is important antigens in early infections, as revealed from ELISA screens with patient IgM sera, highlighting new aspects of glycolipid function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ceramides / metabolism
  • Diglycerides / metabolism
  • Disease
  • Enzyme-Linked Immunosorbent Assay
  • Escherichia coli
  • Eukaryotic Cells / metabolism
  • Glycolipids / biosynthesis
  • Glycolipids / chemistry
  • Glycosyltransferases / metabolism*
  • Humans
  • Immune Sera
  • Immunity / immunology*
  • Lipids / biosynthesis*
  • Lipids / chemistry
  • Magnetic Resonance Spectroscopy
  • Mycoplasma pneumoniae / cytology
  • Mycoplasma pneumoniae / enzymology*
  • Mycoplasma pneumoniae / growth & development
  • Phosphatidylglycerols / metabolism
  • Protein Folding
  • Sequence Analysis, Protein
  • Solubility
  • Substrate Specificity

Substances

  • 1,2-diacylglycerol
  • Ceramides
  • Diglycerides
  • Glycolipids
  • Immune Sera
  • Lipids
  • Phosphatidylglycerols
  • Glycosyltransferases