Introduction to Glycobiology

by Taylor, Maureen E.; Drickamer, Kurt

• ISBN13: 9780199258680
• ISBN10: 0199258686
• Format: Paperback
• Copyright: 2003-01-09
• Publisher: Oxford University Press

Summary

This is the first textbook which introduces the essential elements of glycobiology in a way that is readily accessible to undergraduates and other non-specialists. It will be of wide interest to graduate students, postdoctoral researchers and faculty members in related fields, who want an introduction to this important interdisciplinary field. Coherent stories about what sugars do for cells and organisms are the focus--particularly the importance of glycosylation in protein secretion and stability, cell-cell adhesion and signaling, and innate and adaptive immunity. The ways in which glycobiology explains human disease are discussed throughout the book, giving it a biomedical context. Illustrated throughout with all new custom-drawn figures, the book's simple organization, highlighted terms and annotated key reference lists make it readable and accessible. In addition, all the figures from the book will be available to download free from the companion web site at http://www.oup.com/uk/best.textbooks/biochemistry/glycobiolo

Table of Contents

Concepts of glycobiology	1	(14)
The field of glycobiology encompasses the multiple functions of sugars attached to proteins and lipids	1	(2)
There are three major classes of glycoconjugates	3	(1)
Glycans are composed of monosaccharides with related chemical structures	4	(4)
Glycosidic linkages between monosaccharides exist in multiple configurations	8	(1)
Formation of glycosidic linkages requires energy and is catalysed by specific enzymes	9	(2)
Understanding structure-function relationships for glycans can be more difficult than for other classes of biopolymers	11	(2)
Glycan structures are encoded indirectly in the genome	13	(1)
Summary	14	(1)
N-linked glycosylation	15	(17)
Diverse N-linked glycans have a common core structure	15	(1)
Assembly of N-linked glycans occurs in three major stages	16	(1)
The precursor oligosaccharide for N-linked glycans is assembled on the lipid dolichol	17	(2)
The dolichol-linked precursor oligosaccharide is transferred to asparagine residues of polypeptides	19	(1)
The core oligosaccharide structure is modified by glycosidases and glycosyltransferases	20	(3)
Hybrid structures and polylactosamine sequences are common extensions of the core oligosaccharide	23	(1)
ABO blood groups are determined by the presence of different terminal sugars on glycans of red blood cells	24	(2)
Hundreds of glycosyltransferases generate highly diverse N-linked glycans	26	(1)
The N-linked glycans of an individual glycoprotein are usually heterogeneous	27	(1)
The nature of N-linked glycans attached to an individual glycoprotein is determined by the protein and the cell in which it is expressed	28	(1)
High mannose structures are present in lower eukaryotes, but the glycosylation machinery has evolved to produce complex glycans in higher organisms	29	(1)
N-linked glycans are essential for development of multicellular organisms	30	(1)
Summary	30	(2)
Conformations of oligosaccharides	32	(16)
Three-dimensional structures of oligosaccharides are called conformations	32	(1)
Monosaccharides assume a limited number of conformations	33	(1)
Torsion angles are used to describe conformations of glycans	33	(3)
Local steric and electronic interactions limit the possible conformations of glycosidic linkages	36	(2)
The conformation of an oligosaccharide is influenced by interactions between hexoses distant from each other in the covalent structure	38	(2)
Co-operative interactions determine the overall folds of oligosaccharides	40	(3)
Oligosaccharide conformations are dynamic	43	(1)
Short- and long-range interactions also determine the conformations of polysaccharides	43	(1)
The conformations of a small number of oligosaccharides have been analysed by X-ray crystallography and nuclear magnetic resonance	44	(2)
Summary	46	(2)
Strategies for analysis of glycan structures	48	(10)
Enzymes are used to analyse structures of N-linked glycans	48	(3)
Isolated oligosaccharides and intact glycoconjugates can be analysed with lectins	51	(1)
Mass spectrometry and nuclear magnetic resonance spectroscopy are useful physical methods for establishing glycan structures	52	(1)
Small oligosaccharides can be synthesized using chemical methods	52	(2)
Enzymes provide an alternative method for the synthesis of oligosaccharides	54	(1)
Neoglycoconjugates can be created by chemically linking sugars to proteins or lipids	55	(2)
Summary	57	(1)
O-linked glycosylation	58	(22)
Mucins are large, heavily O-glycosylated proteins that hold water	58	(3)
Some cell surface proteins have mucin-like domains	61	(2)
Many soluble and cell surface glycoproteins contain small clusters of O-linked sugars	63	(1)
Biosynthesis of mucin-type sugars occurs by sequential addition of monosaccharides to proteins in the Golgi apparatus	64	(1)
Proteoglycans are heavily O-glycosylated proteins that give strength to the extracellular matrix	65	(2)
Cell surface proteoglycans interact with growth factors	67	(3)
Biosynthesis of proteoglycans requires several modifying enzymes in addition to glycosyltransferases	70	(1)
O-linked fucose-based glycans are important for extracellular signalling during development	71	(3)
Unusual types of O-linked glycosylation are found on some proteins	74	(1)
Cytoplasmic and nuclear proteins can be modified by addition of O-linked N-acetylglucosamine	75	(3)
Summary	78	(2)
Glycolipids and membrane protein glycosylation	80	(17)
Most integral membrane proteins are glycosylated	80	(2)
Polysialylation of neural cell adhesion molecule prevents cell adhesion	82	(1)
Membranes contain glycolipids as well as glycoproteins	83	(1)
Glycosphingolipid biosynthesis occurs in the Golgi apparatus	84	(2)
Cell surface glycolipids are important for the development of the nervous system	86	(2)
Defects in glycolipid breakdown cause disease	88	(1)
Some proteins are attached to membranes through glycolipid anchors	89	(2)
Glycolipid anchors are added to proteins in the endoplasmic reticulum	91	(1)
Proteins attached to glycolipid anchors are localized to the plasma membrane	92	(1)
The disease paroxysmal nocturnal haemoglobinuria is caused by a glycolipid anchor deficiency	93	(1)
Summary	94	(3)
Effects of glycosylation on protein structure and function	97	(14)
Various approaches can be used to study the effects of glycosylation	97	(2)
Sugars stabilize the structure of the cell adhesion molecule CD2	99	(2)
An oligosaccharide replaces an α-helix in some variant surface glycoproteins of trypanosomes	101	(2)
Attachment of a monosaccharide can increase protein stability	103	(1)
The stability of ribonuclease is increased by N-glycosylation	104	(2)
Protein-protein interactions can be modulated by oligosaccharides	106	(1)
Oligosaccharides covering surfaces can protect against proteolysis	107	(2)
Summary	109	(2)
Glycoprotein trafficking in cells and organisms	111	(17)
Animal lectins have diverse structures and functions	111	(1)
Lectins have important functions in the secretory pathway	112	(1)
Calnexin and calreticulin help glycoproteins fold in the endoplasmic reticulum	113	(1)
Lectins are involved in degradation of misfolded glycoproteins	114	(1)
L-type lectins transport glycoproteins from the endoplasmic reticulum to the Golgi	115	(2)
Mannose 6-phosphate residues target lysosomal enzymes to lysosomes	117	(2)
Two types of mannose 6-phosphate receptor take part in lysosomal enzyme targeting	119	(2)
The asialoglycoprotein receptor clears altered serum glycoproteins into the liver	121	(1)
The mannose receptor removes naturally occurring glycoproteins from circulation	122	(2)
The mannose receptor also regulates activity of sulphated hormones	124	(1)
Some intracellular lectins have roles in the nucleus	125	(1)
Summary	125	(3)
Carbohydrate recognition in cell adhesion and signalling	128	(25)
The selectins are cell adhesion molecules for white blood cells	128	(3)
Specific carbohydrate ligands for the selectins have been identified	131	(2)
The selectins are also signal transduction molecules	133	(1)
C-type lectins participate in the process of antigen presentation	134	(1)
DC-SIGN and DC-SIGNR enhance human immunodeficiency virus infection of T cells	135	(2)
The siglecs are cell adhesion and signalling molecules	137	(1)
Sialoadhesin is an adhesion receptor on macrophages	137	(3)
Myelin-associated glycoprotein has roles in the central and peripheral nervous systems	140	(1)
CD22 is a signalling molecule on B cells	141	(1)
Extracellular galectins have roles in cell adhesion and cell signalling	141	(4)
Mannose-binding protein is a host defence molecule	145	(1)
Mannose-binding protein initiates the lectin pathway of complement activation	146	(2)
The mannose receptor helps macrophages to internalize pathogens	148	(2)
Summary	150	(3)
Mechanisms of sugar recognition in animal lectins	153	(14)
Lectin classification is based on primary structure	153	(1)
C-type carbohydrate-recognition domains bind two hydroxyl groups of a monosaccharide in complex with Ca2+	154	(2)
A small number of residues in a C-type carbohydrate-recognition domain determines the types of ligand that are bound	156	(2)
Some features of monosaccharide binding are similar in all types of carbohydrate-recognition domains	158	(1)
Binding of oligosaccharide ligands to the selectins requires additional interactions with the carbohydrate-recognition domains	159	(2)
Extended binding sites are found in many lectins	161	(2)
Valency and oligomer geometry determine specificity and affinity of lectins for oligosaccharides	163	(2)
Summary	165	(2)
Glycobiology of plants, bacteria, and viruses	167	(16)
Plant and microbial glycans have some functions not seen in mammals	167	(1)
Plants use oligosaccharides as signalling molecules	168	(2)
Common plant lectins are useful tools for biologists	170	(2)
Some plant lectins are toxins	172	(2)
Many bacterial toxins are lectins	174	(1)
Bacteria use lectins to bind to host cell surfaces	175	(2)
Viruses use lectins to target cell surfaces	177	(2)
Lectins appeared early in evolution but have diverse functions in higher organisms	179	(2)
Summary	181	(2)
Glycosylation and disease	183	(14)
Mutations in enzymes for synthesis of N-linked glycans cause congenital disorders of glycosylation	183	(2)
Abnormal expression of a glycosyltransferase causes a blood clotting defect	185	(2)
Chemical glycation of proteins occurs in diabetes	187	(1)
Antibodies to carbohydrates can cause disease	188	(1)
IgG glycosylation is altered in rheumatoid arthritis	189	(2)
Changes in glycosylation are associated with cancer	191	(2)
Monitoring changes in glycosylation may be useful for cancer detection and treatment	193	(2)
Summary	195	(2)
The future of glycobiology	197	(6)
Important clues about roles for specific glycans will continue to come from biochemical and genetic studies	197	(2)
Genomics is starting to provide new insights into glycobiology	199	(1)
Glycomics promises a global view of glycobiology	199	(1)
Model organisms will be most useful in the analysis of more primitive functions of glycosylation	200	(1)
Molecular understanding of how glycans function will require further elucidation of structure-function relationships	201	(1)
Our increasing knowledge about glycobiology is being applied to practical issues	201	(1)
Summary	201	(2)
Index	203