Spatial structures of glycan chains of glycoproteins in relation to metabolism and function. Survey of a decade of research
Ab4t'uw.t Thanks to the progress in chemical and enzymatic methodologies, and to the use of high-resolution NMR spectroscopy the primary structure of hundreds of glycoprotein glycans has been determined. The knowledge acquired in this field has been decisive in the elucidation of the mechanisms of glycoprotein biosynthesis and of their regulation, and in a better understanding of their biological roles. In this connection, the determination of the spatial configuration became a necessity. Ten years ago, future results were anticipated by building the Y-shaped molecular model of a biantenmary glycan. Little by little, this structure has been refined and modified thanks to experimental data obtained by using physical methods : X-ray diffraction, EPR, NMR, including two-dimensional NMR and onedimensional 1H—nuclear Overhauser effect (NOE) experiments, neutron scattering and hard-sphere CXO—anomeric (HSEA) calculations. So, the concept evolved successively from the Y—, to the T-, the bird— and the 'broken wing"conformation, until the demonstration that these conformers are interconvertible. The birdconformation as well as the concept of the mobility of antennae are in a good agreement with the reactivity of lectins, including membrane lectins, by rendering accessible any specific sugar structure, and with the activity of glycosyltransfe— rases by making attainable the substituable hydroxyl groups even in the case of pentaantennary structures. In the same way, we know now that the tetraantennary glycans adopt an "umbrella conformation" in which the four antennae are disposed parallely to the protein surface and act as protective shields. So could be explained the resistance towards proteases and the weak antigenicity of numerous glycoproteins as well as the peculiar behaviour and resistance of metastatic cancerous cells since it has been recently demonstrated that membrane glycoproteins and fibronectin of this kind of cells are significantly enriched in tnand tetraantennary glycans.