Post-translational modifications to Toxoplasma gondii alpha- and beta-tubulins include novel C-terminal methylation

J Proteome Res. 2010 Jan;9(1):359-72. doi: 10.1021/pr900699a.

Abstract

Toxoplasma gondii is an apicomplexan of both medical and veterinary importance which is classified as an NIH Category B priority pathogen. It is best known for its ability to cause congenital infection in immune competent hosts and encephalitis in immune compromised hosts. The highly stable and specialized microtubule-based cytoskeleton participates in the invasion process. The genome encodes three isoforms of both alpha- and beta-tubulin and we show that the tubulin is extensively altered by specific post-translational modifications (PTMs) in this paper. T. gondii tubulin PTMs were analyzed by mass spectrometry and immunolabeling using specific antibodies. The PTMs identified on alpha-tubulin included acetylation of Lys40, removal of the last C-terminal amino acid residue Tyr453 (detyrosinated tubulin) and truncation of the last five amino acid residues. Polyglutamylation was detected on both alpha- and beta-tubulins. An antibody directed against mammalian alpha-tubulin lacking the last two C-terminal residues (Delta2-tubulin) labeled the apical region of this parasite. Detyrosinated tubulin was diffusely present in subpellicular microtubules and displayed an apparent accumulation at the basal end. Methylation, a PTM not previously described on tubulin, was also detected. Methylated tubulins were not detected in the host cells, human foreskin fibroblasts, suggesting that this may be a modification specific to the Apicomplexa.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Cytoskeleton / chemistry
  • Cytoskeleton / metabolism*
  • Electrophoresis, Gel, Two-Dimensional
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism
  • Methylation
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptides
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Processing, Post-Translational*
  • Proteomics / methods
  • Sequence Alignment
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Toxoplasma / chemistry
  • Toxoplasma / metabolism*
  • Tubulin / chemistry
  • Tubulin / metabolism*

Substances

  • Membrane Proteins
  • Peptide Fragments
  • Peptides
  • Protein Isoforms
  • Tubulin
  • polyglutamine