Lipoarabinomannans: characterization of the multiacylated forms of the phosphatidyl-myo-inositol anchor by NMR spectroscopy

Lipoarabinomannans, which exhibit a large spectrum of immunological activities, emerge as the major antigens of mycobacterial envelopes. The lipoarabinomannan structure is based on a phosphatidyl-myo-inositol anchor whose integrity has been shown to be crucial for lipoarabinomannan biological activi...

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Bibliographic Details
Published in:Biochemical journal 1999-02, Vol.337 ( Pt 3) (3), p.453-460
Main Authors: Nigou, J, Gilleron, M, Puzo, G
Format: Article
Language:English
Subjects:
Biochemistry, Molecular Biology
Carbohydrate Sequence
Life Sciences
Lipopolysaccharides
Lipopolysaccharides - chemistry
Magnetic Resonance Spectroscopy
Mannose
Mannose - chemistry
Molecular Sequence Data
Mycobacterium bovis
Mycobacterium bovis - chemistry
Phosphatidylinositols
Phosphatidylinositols - chemistry
Structural Biology
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Summary:Lipoarabinomannans, which exhibit a large spectrum of immunological activities, emerge as the major antigens of mycobacterial envelopes. The lipoarabinomannan structure is based on a phosphatidyl-myo-inositol anchor whose integrity has been shown to be crucial for lipoarabinomannan biological activity and particularly for presentation to CD4/CD8 double-negative alphabetaT cells by CD1 molecules. In this report, an analytical approach was developed for high-resolution 31P-NMR analysis of native, i.e. multiacylated, lipoarabinomannans. The one-dimensional 31P spectrum of cellular lipoarabinomannans, from Mycobacterium bovis Bacillus Calmette-Guérin, exhibited four 31P resonances typifying four types of lipoarabinomannans. Two-dimensional 1H-31P heteronuclear multiple-quantum-correlation/homonuclear Hartmann-Hahn analysis of the native molecules showed that these four types of lipoarabinomannan differed in the number and localization of fatty acids (from 1 to 4) esterifying the anchor. Besides the three acylation sites previously described, i.e. positions 1 and 2 of glycerol and 6 of the mannosyl unit linked to the C-2 of myo-inositol, we demonstrate the existence of a fourth acylation position at the C-3 of myo-inositol. We report here the first structural study of native multiacylated lipoarabinomannans, establishing the structure of the intact phosphatidyl-myo-inositol anchor. Our findings would help gain more understanding of the molecular basis of lipoarabinomannan discrimination in the binding process to CD1 molecules.
ISSN:0264-6021
1470-8728
DOI:10.1042/0264-6021:3370453