Killing of Trypanosoma brucei by Concanavalin A: Structural basis of resistance in glycosylation mutants

Alvaro Acosta-Serrano, Robert N. Cole, Paul T. Englund

Research output: Contribution to journalArticle

Abstract

Concanavalin A (Con A) kills procyclic (insect) forms of Trypanosoma brucei by binding to N-glycans on EP-procyclin, a major surface glycosyl phosphatidylinositol (GPI)-anchored protein which is rich in Glu-Pro repeats. We have previously isolated and studied two procyclic mutants (ConA 1-1 and ConA 4-1) that are more resistant than wild-type (WT) to Con A killing. Although both mutants express the same altered oligosaccharides compared to WT cells, ConA 4-1 is considerably more resistant to lectin killing than is ConA 1-1. Thus, we looked for other alterations to account for the differences in sensitivity. Using mass spectrometry, together with chemical and enzymatic treatments, we found that both mutants express types of EP-procyclin that are either poorly expressed or not found at all in WT cells. ConA 1-1 expresses mainly EP1-3, a novel procyclin that contains 18 EP repeats, is partially N-glycosylated, and bears hybrid-type glycans. On the other hand, ConA 4-1 cells express almost exclusively EP2-3, a novel non-glycosylated procyclin isoform with 23 EP repeats and no site for glycosylation. The predominance of EP2-3 in ConA 4-1 cells explains their high resistance to ConA killing. Thus, switching the procyclin repertoire, a process that could be relevant to parasite development in the insect vector, modulates the sensitivity of trypanosomes to cytotoxic lectins. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)633-644
Number of pages12
JournalJournal of molecular biology
Volume304
Issue number4
DOIs
StatePublished - Dec 8 2000

Keywords

  • Glycosyl phosphatidylinositol
  • Mass spectrometry
  • N-glycosylation
  • Procyclin
  • Trypanosome

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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