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Primary sequence dependence of conformation in oligomannose oligosaccharides

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Abstract

The oligomannose series of oligosaccharides from bovine thyroglobulin (BTG) and the variant surface glycoprotein (VSG) ofTrypanosoma brucei have been isolated and sequenced by1H NMR. The structure of Man9GlcNAc2, the parent molecule of the series, is shown below. Structural isomerism occurs within this series through the removal of residues D1, D2, D3, and C. Using spin-spin coupling and chemical shift data the rotamer distributions about the dihedral angle ω for the Manα1-6Man\ and Manα1-6Manα linkages were determined for each member of the series. It is shown that the dihedral angle ω of the Manα1-6Man\ linkage exhibits low flexibility with a preference for the ω = 180° conformation when residue D2 is present and high flexibility when this residue is absent. Flexibility of ω for the Manα1-6Manα is largely independent of primary sequence and is intermediate between the two Manoα1-6Man\ extremes, again with a preference for the ω = 180° conformation.

There are, however, data which indicate that removal of residue D3 may confer additional flexibility upon the dihedral angle ω of the Manα1-6Manα linkage. Molecular graphics modelling, together with chemical and enzymatic modification studies, suggest that the origin of the observed primary sequence dependence of the Manα1-6Man\ linkage arises from steric factors. On the basis of these observations taken together with previous work, it is postulated that recognition of individual oligomannose conformations may play a role in the control of N-linked oligosaccharide biosynthesis.

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Abbreviations

AMBER:

assisted model building with energy refinement

BTG:

bovine thyroglobulin

COSY:

1H-1H correlation spectroscopy

Endo-H:

endo-β-N-acetylglucosaminidase H

NMR:

nuclear magnetic resonance

NOE:

nuclear Overhauser effect

NOESY:

two dimensional1H-1H nuclear Overhauser effect spectroscopy

HOHAHA:

homonuclear Hartmann-Hahn spectroscopy

HSEA:

hard sphere exo-anomeric effect, RECSY, multistep relayed correlation spectroscopy

VSG:

variant surface glycoprotein

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Authors and Affiliations

  1. Oxford Glycobiology Unit, University of Oxford, OX1 3QU, Oxford, United Kingdom

    E. W. Wooten, R. Bazzo, C. J. Edge, S. Zamze, R. A. Dwek & T. W. Rademacher

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  1. E. W. Wooten
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  2. R. Bazzo
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  3. C. J. Edge
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  4. S. Zamze
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  5. R. A. Dwek
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  6. T. W. Rademacher
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Wooten, E.W., Bazzo, R., Edge, C.J. et al. Primary sequence dependence of conformation in oligomannose oligosaccharides. Eur Biophys J 18, 139–148 (1990). https://doi.org/10.1007/BF02427373

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  • DOI: https://doi.org/10.1007/BF02427373

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