UNIVERSITY OF BUCHAREST
FACULTY OF PHYSICS

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Conference: Bucharest University Faculty of Physics 2004 Meeting


Section: Electricity and Biophysics


Title:
A statistical analysis of N-glycosylation sites. Implications for glycan roles in glycoprotein structure and folding


Authors:
Adina-L. Milac2 , Stefana M. Petrescu1,2, Raymond A. Dwek1, Mark R. Wormald1, and Andrei-J. Petrescu1,2


Affiliation:
1 Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South

Parks Road, Oxford OX1 3QU, UK.

2 Institute of Biochemistry of the Romanian Academy, Spl. Independentei 296, 77700, Bucharest 17, Romania.


E-mail


Keywords:


Abstract:
Based on an up to date survey of the available crystallographic data we have generated a database of structural parameters of glycans and glycoproteins (1). Using these data, we have performed a statistical analysis of the glycosidic and Asn-NAG linkages in N-linked oligosaccarides and of the structural properties of the protein moiety around the N-glycosylation sites. We have surveyed 506 glycoproteins in the PDB crystallographic database giving 2592 glycosylation sequons, 1683 occupied, and generated a set of 626 non-redundant sequons with 386 occupied. Deviations in the expected amino acid composition were seen around occupied asparagines, particularly an increased occurrence of aromatic residues before the asparagine and threonine at position +2. Glycosylation alters the asparagine side chain torsion angle distribution and reduces its flexibility. There is an elevated probability of finding glycosylation sites where secondary structure changes. An 11 class taxonomy was developed to describe protein surface geometry around glycosylation sites. 33% of the occupied sites are on exposed convex surfaces, 10% in deep recesses and 20% on the edge of grooves with the glycan filling the cleft. A surprisingly large number of glycosylated asparagine residues have a low accessibility. The incidence of aromatic amino acids brought into close contact with the glycan by the folding process is higher than their normal levels on the surface or in the protein core. These data have significant implications for control of sequon occupancy and evolutionary selection of glycosylation sites, and suggest mechanisms of protein fold stabilisation and regional quality control of protein folding. Hydrophobic protein-glycan interactions and the low accessibility of glycosylation sites in folded proteins are common features and may be critical in mediating these functions.