Acylated-acyl carrier protein stabilizes the Pseudomonas aeruginosa WaaP lipopolysaccharide heptose kinase

Sci Rep. 2018 Sep 20;8(1):14124. doi: 10.1038/s41598-018-32379-1.

Abstract

Phosphorylation of Pseudomonas aeruginosa lipopolysaccharide (LPS) is important for maintaining outer membrane integrity and intrinsic antibiotic resistance. We solved the crystal structure of the LPS heptose kinase WaaP, which is essential for growth of P. aeruginosa. WaaP was structurally similar to eukaryotic protein kinases and, intriguingly, was complexed with acylated-acyl carrier protein (acyl-ACP). WaaP produced by in vitro transcription-translation was insoluble unless acyl-ACP was present. WaaP variants designed to perturb the acyl-ACP interaction were less stable in cells and exhibited reduced kinase function. Mass spectrometry identified myristyl-ACP as the likely physiological binding partner for WaaP in P. aeruginosa. Together, these results demonstrate that acyl-ACP is required for WaaP protein solubility and kinase function. To the best of our knowledge, this is the first report describing acyl-ACP in the role of a cofactor necessary for the production and stability of a protein partner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyl Carrier Protein / metabolism*
  • Acylation
  • Bacterial Proteins / metabolism*
  • Lipopolysaccharides / metabolism*
  • Pseudomonas aeruginosa / metabolism*

Substances

  • Acyl Carrier Protein
  • Bacterial Proteins
  • Lipopolysaccharides