Structure of Leishmania lipophosphoglycan: Inter- and intra-specific polymorphism in Old World species

M. J. McConville*, L. F. Schnur, C. Jaffe, P. Schneider

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

The most abundant surface macromolecule on the promastigote stage of leishmanial parasites is a polymorphic lipophosphoglycan (LPG). We have elucidated the structures of two new LPGs, from Leishmania tropica (LRC-L36) and L. aethiopica (LRC-L495), and investigated the nature of intra-specific polymorphism in the previously characterized LPG of L. major (LRC-L456 and -L580). These molecules contain a phosphoglycan chain, made up of repeating PO4-6Galβ1-4Man units and a conserved hexaglycosyl-phosphatidylinositol membrane anchor. Extensive polymorphism occurs in the extent to which the LPG repeat units are substituted with different glycan side chains. The L. tropica LPG is the most complex LPG characterized to date, as most of the repeat units are substituted with more than 19 different glycan side chains. All of these side chains, including the novel major glycans, Arapβ1-3Glcβ1- and ± Arapβ1-2Glcβ1-4[± Arapβ1-2]Glcβ1-, are linked to the C-3 position of the backbone disaccharide galactose. In contrast, the L. aethiopica LPG repeat units are partially substituted (35%) with single α-mannose residues that are linked, unusually, to the C-2 position of the mannose in the backbone disaccharide. Polymorphism is also evident in the spectrum of α-mannose-containing oligosaccharides that cap the non-reducing terminus of the phosphoglycan chains of these LPGs. Finally, analysis of the L. major LPGs showed that, while some strains contain LPGs which are highly substituted with side chains of βGal, Galβ1-3Galβ1- and Arapβ1-2Galβ1-3Galβ1-, the LPGs of other strains (i.e L. major LRC-L456) are essentially unsubstituted. Recent studies have shown that the LPG side chains and cap structures can mediate promastigote attachment to a number of different receptors along the midgut of the sandfly vector. The possible significance of LPG polymorphism on the ability of these parasites to infect a number of different sandfly vectors is discussed.

Original languageEnglish
Pages (from-to)807-818
Number of pages12
JournalBiochemical Journal
Volume310
Issue number3
DOIs
StatePublished - 1995
Externally publishedYes

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