CHAPTER 23
Exploring Functions for Glycosylation in Host Defence
using Novel Oligosaccharide Sequencing Technology
P. M. RUDD 1 , M. R. WORMALD 1 and R. A. DWEKI
1
Abstract
A full understanding of the implications of glycosylation for the structure and
function of any glycoprotein can only be reached when the molecule is viewed in
its entirety. NMR solution and X-ray crystallography studies of glycoproteins do
not normally yield detailed information about the sugars. Here protein structural
data have been complemented by oligosaccharide analysis of the sugars released
from 5-101lg of protein. The data discussed in this paper were obtained using
rapid glycan sequencing technology and the linkage structure data base (both
developed in the Institute), which provides the dimensions of the sugars. In this
way it has been possible to obtain a more complete view of some glycoproteins in
the immune system and the roles which the oligo saccharides play in their functions. Roles for the sugars include stabilising the protein structure, modifying the
activity of effector functions, orienting the protein on the cell surface, shielding
the protein from proteases and providing specific epitopes for recognition events.
The glycoproteins which will be discussed include the immunoglobulins IgG and
IgAl, the inhibitors of the complement pathway CD59 and DAF (CD55), and the
cell adhesion molecules CD2 and CD48. CD2 and CD48 mediate the alignment of
the cell surfaces of cytolytic T-Iymphocytes carrying the TCR complex with those
of target cells carrying loaded HLA class 1 molecules.
2
Introduction
Mammals have developed a variety of strategies with which to respond to the
challenges posed by pathogenic viruses or bacteria. These organisms can replicate in the blood or mucosa or have evolved mechanisms for invading and replicating in host cells. A key event in every immune response to infection involves
functional recognition of foreign proteins or lipids. Many proteins involved in the
immune response are glycosylated, and the awareness of the importance of the
attached sugars in the function of these molecules is increasing. By combining
I Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road,
Oxford, OXl 3QU, UK.
Exploring Functions for Glycosylation in Host Defence
using Novel Oligosaccharide Sequencing Technology
P. M. RUDD 1 , M. R. WORMALD 1 and R. A. DWEKI
1
Abstract
A full understanding of the implications of glycosylation for the structure and
function of any glycoprotein can only be reached when the molecule is viewed in
its entirety. NMR solution and X-ray crystallography studies of glycoproteins do
not normally yield detailed information about the sugars. Here protein structural
data have been complemented by oligosaccharide analysis of the sugars released
from 5-101lg of protein. The data discussed in this paper were obtained using
rapid glycan sequencing technology and the linkage structure data base (both
developed in the Institute), which provides the dimensions of the sugars. In this
way it has been possible to obtain a more complete view of some glycoproteins in
the immune system and the roles which the oligo saccharides play in their functions. Roles for the sugars include stabilising the protein structure, modifying the
activity of effector functions, orienting the protein on the cell surface, shielding
the protein from proteases and providing specific epitopes for recognition events.
The glycoproteins which will be discussed include the immunoglobulins IgG and
IgAl, the inhibitors of the complement pathway CD59 and DAF (CD55), and the
cell adhesion molecules CD2 and CD48. CD2 and CD48 mediate the alignment of
the cell surfaces of cytolytic T-Iymphocytes carrying the TCR complex with those
of target cells carrying loaded HLA class 1 molecules.
2
Introduction
Mammals have developed a variety of strategies with which to respond to the
challenges posed by pathogenic viruses or bacteria. These organisms can replicate in the blood or mucosa or have evolved mechanisms for invading and replicating in host cells. A key event in every immune response to infection involves
functional recognition of foreign proteins or lipids. Many proteins involved in the
immune response are glycosylated, and the awareness of the importance of the
attached sugars in the function of these molecules is increasing. By combining
I Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road,
Oxford, OXl 3QU, UK.