Myristate exchange. A second glycosyl phosphatidylinositol myristoylation reaction in African trypanosomes

L. U. Buxbaum, J. Raper, F. R. Opperdoes, P. T. Englund

Research output: Contribution to journalArticlepeer-review

Abstract

The variant surface glycoprotein of African trypanosomes has a glycosyl phosphatidylinositol (GPI) anchor that is unusual in that its fatty acids are exclusively myristate. We showed previously that the myristate is added to a free GPI in a fatty acid remodeling reaction involving deacylation and reacylation, forming glycolipid A, the anchor precursor. We now demonstrate that trypanosomes have a second pathway for GPI anchor myristoylation distinct from the fatty acid remodeling pathway, which we call 'myristate exchange.' This reaction involves exchange of myristate into both the sn-1 and sn-2 positions of glycolipid A, which already contain myristate. Myristoyl-CoA, the probable myristate donor in the exchange reaction, has an apparent K(m) of about 6 nM. We have now identified a lyso-GPI, named θ', which has myristate as its sole fatty acid; the kinetics of formation and utilization of θ' are consistent with it being an intermediate in exchange. Myristate exchange and fatty acid remodeling appear to occur in different subcellular compartments, and the two reactions have different sensitivities to inhibitors. The myristate exchange reaction may be a proofreading system to ensure that the fatty acids on variant surface glycoproteins are exclusively myristate.

Original languageEnglish (US)
Pages (from-to)30212-30220
Number of pages9
JournalJournal of Biological Chemistry
Volume269
Issue number48
StatePublished - Jan 1 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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