Oral Presentation 29th Annual Lorne Proteomics Symposium 2024

Monoclonal antibody tools for protein pseudaminylation (#31)

Ethan D Goddard-Borger 1 , Richard J Payne 2 , Nichollas E Scott 3
  1. Walter and Eliza Hall Institute, Parkville, VIC, Australia
  2. School of Chemistry, The University of Sydney, Sydney, NSW, Australia
  3. Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC, Australia

Pseudaminic acid is a nonulosonic acid used by diverse bacterial phyla to modify proteins, capsular polysaccharides, and lipopolysaccharide. It is an important virulence factor for pathogens like C. jejuni and H. pylori, where it is essential for bacterial motility. To date, this protein modification has only been described on a small number of proteins: a more complete view of protein pseudaminylation requires the development of a suitable enrichment method.

To that end, we raised monoclonal antibodies against pseudaminylated peptides. The affinities and binding kinetics of these antibodies were determined, and their molecular interactions with pseudaminic acid investigated through structural studies. The specificity of these tools was further confirmed using bacterial strains lacking pseudaminic acid. These antibodies were then used to immunoprecipitate pseudaminylated peptides from a diverse collection of bacteria for glycoproteomic analyses. This identified many new proteins with pseudaminylation sites and provides new avenues to explore the biology of this unusual protein modification.