Protein Glycosylation: Implications for In Vivo Functions and Therapeutic Applications - Advances in Biochemical Engineering Biotechnology - page 152

Protein Glycosylation: Implications for In Vivo
Functions and Therapeutic Applications

Prakash K. Bhatia 1,3 · Asok Mukhopadhyay 2

1 National Institute of Immunology,Aruna Asaf Ali Marg, New Delhi-110 067, India
2 National Institute of Immunology,Aruna Asaf Ali Marg, New Delhi-110 067, India.
E-mail: [e-mail]
3 499, Sector 11, Hiranmagri, Udaipur 313001, India

The glycosylation machinery in eukaryotic cells is available to all proteins that enter the secre-
tory pathway. There is a growing interest in diseases caused by defective glycosylation, and in
therapeutic glycoproteins produced through recombinant DNA technology route. The choice
of a bioprocess for commercial production of recombinant glycoprotein is determined by a
variety of factors,such as intrinsic biological properties of the protein being expressed and the
purpose for which it is intended,and also the economic target.This review summarizes recent
development and understanding related to synthesis of glycans, their functions, diseases, and
various expression systems and characterization of glycans. The second section covers
processing of N - and O -glycans and the factors that regulate protein glycosylation. The third
section deals with in vivo functions of protein glycosylation, which includes protein folding
and stability, receptor functioning, cell adhesion and signal transduction. Malfunctioning of
glycosylation machinery and the resultant diseases are the subject of the fourth section. The
next section covers the various expression systems exploited for the glycoproteins: it includes
yeasts, mammalian cells, insect cells, plants and an amoeboid organism. Biopharmaceutical
properties of therapeutic proteins are discussed in the sixth section. In vitro protein glyco-
sylation and the characterization of glycan structures are the subject matters for the last
two sections, respectively.

Keywords: Glycoprotein, Protein stability, Disease, Expression, Half-life.

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157

2 Site and Events of Glycosylation in Eukaryotic Cells . . . . . . . . 158
2.1 Entry in the Secretory Route . . . . . . . . . . . . . . . . . . . . . . 158
2.2 Early Modifications of Protein . . . . . . . . . . . . . . . . . . . . . 159
2.3 Asparagine-Linked Glycosylation . . . . . . . . . . . . . . . . . . . 160
2.3.1 Biosynthesis and Processing . . . . . . . . . . . . . . . . . . . . . . 162
2.3.2 Factors Regulating Asn-Linked Glycosylation . . . . . . . . . . . . 166
2.4 The Biosynthesis of Ser/ Thr-Linked Glycans . . . . . . . . . . . . . 167

2.5 Glucosylphosphatidylinositol (GPI) Anchors . . . . . . . . . . . . . 168

3 Functions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169

3.1 Protein Folding and Conformation . . . . . . . . . . . . . . . . . . 169

3.2 Protein Stabilization and Structural Integrity . . . . . . . . . . . . 170

3.3 Receptor Functioning . . . . . . . . . . . . . . . . . . . . . . . . . . 172

3.4 Intracellular Trafficking . . . . . . . . . . . . . . . . . . . . . . . . 173