Copyright © 1998, CRC Press LLC — Files may be downloaded for personal use only. Reproduction of this material without the consent of the publisher is prohibited. 151 Critical Reviews in Biochemistry and Molecular Biology, 33(3):151–208 (1998) Concepts and Principles of O-Linked Glycosylation Philippe Van den Steen, 1 Pauline M. Rudd, 2 Raymond A. Dwek, 2 and Ghislain Opdenakker 1,2 1 Rega Institute, Molecular Immunology, Department of Microbiology and Immunology, University of Leuven, Belgium; 2 Glycobiology Institute, Department of Biochemistry, University of Oxford, UK TABLE OF CONTENTS I. Introduction ................................................................................................................... 151 II. Structures and Biosynthesis of O-Linked Glycans .................................................... 157 A. Introduction ................................................................................................................. 157 B. Biosynthesis of Mucin-Type O-Glycans .................................................................... 158 1. Addition of the First GalNAc ............................................................................... 158 2. Biosynthesis of the Core Structures and Further Elongation and Termination ..................................................................................................... 160 C. Non-Mucin O-Linked Sugars in Mammals ................................................................ 162 D. Biosynthesis of O-Linked Sugars in the Yeast Saccharomyces cerevisiae .............. 164 III. Effects of O-Linked Glycosylation on Protein Structure and Stability .................. 165 A. O-Glycans Maintain Tertiary Structure ...................................................................... 165 B. O-Glycans Modulate Aggregation .............................................................................. 167 C. O-Glycans Maintain Protein Stability and Confer Protease and Heat Resistance ........................................................................................................... 167 IV. O-Linked Glycosylation Functions in Recognition .................................................... 168 A. O-Linked Glycosylation of Selectin Ligands ............................................................. 168 B. Function of O-Linked Oligosaccharides in Fertilization ........................................... 171 C. O-Linked Glycosylation in Specific Immunological Recognition ............................ 173 D. Influence of O-Linked Glycosylation on Glycoprotein Clearance ............................ 178 E. Other Examples of O-Linked Structures and Recognition ........................................ 179 F. Multivalent and Multimeric Binding and Signal Transduction ................................. 179 V. O-Linked Glycosylation Influences the Activity of Signaling Molecules . ............... 181 VI. Effects of O-Linked Glycosylation on the Activity of Enzymes . ............................. 183 VII. The Role of Ser/Thr-Rich Domains . ........................................................................... 184 A. Ser/Thr-Rich Domains on Cell Surface Glycoproteins ............................................. 184 B. Ser/Thr-Rich Domains of Immunoglobulins .............................................................. 185 VIII. Role of O-Linked Glycosylation in Protein Expression and Processing . ................ 187 Critical Reviews in Biochemistry and Molecular Biology Downloaded from informahealthcare.com by 183.223.29.58 on 05/20/14 For personal use only.