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Essentials of Glycobiology
Editors: Ajit Varki, Richard Cummings, Jeffrey Esko, Hudson Freeze, Gerald Hart, and Jamey Marth.
Excerpt
Emerging from its roots in classical carbohydrate chemistry and biochemistry, glycobiology has become a vibrant, expanding, and important extension of modern molecular biology. Over the years, many outstanding monographs and books have documented important advances in this area and summarized critical methods and concepts. These volumes continue to serve as excellent resources for those interested in glycobiology. Why then should one publish an additional book on the subject? Most of these prior volumes have been directed at the specialist, assuming a substantial level of technical sophistication and expertise and a working knowledge of the relevant jargon. We present here a book that seeks to fulfill a somewhat different need: to summarize the current state of the art for the expert and yet serve as a resource for the novice wishing to explore the essentials of glycobiology.
Contents
- Dedication
- Foreword
- Preface
- Contributors
- Symbolic Representations of Common Monosaccharides and Linkages
- Abbreviations
- General Principles
- Chapter 1. Historical Background and Overview
- What Is Glycobiology?
- Monosaccharides Are the Basic Structural Units of Glycans
- Glycans Can Constitute a Major Portion of a Glycoconjugate
- Monosaccharides Generate More Linkage Variation Than Amino Acids or Nucleotides
- Common Monosaccharide Units of Animal Glycoconjugates
- Major Classes of Glycoconjugates and Oligosaccharides
- Topological Issues Relevant to the Biosynthesis of Glycans
- Nuclear and Cytoplasmic Glycosylation Is Common
- Outer Structures Are Often Shared among Classes of Glycans
- Microheterogeneity: A Common Feature of Protein Glycosylation
- Turnover and Degradation of Glycans
- Tools Used to Study Glycosylation
- Genetic Glycosylation Defects in Cultured Cells and Intact Animals
- Biological Roles of Glycans Appear to Be Diverse
- Glycosylation Changes in Development, Differentiation, Malignancy, and Phylogeny
- Glycobiology in Biotechnology and Medicine
- References
- Chapter 2. Saccharide Structure and Nomenclature
- Chapter 3. Evolution of Glycan Diversity
- Relatively Little Is Known about Glycan Diversity in Nature
- Evolution of the N-Glycan Processing Pathway
- Evolutionary Distribution of O-Glycans
- Evolutionary Distribution of Glycosphingolipids
- Diversity of Sialic Acids in Evolution
- Evolutionary Distribution of Glycosaminoglycan Chains
- Evolutionary Distribution of Glycophospholipid Anchors
- Evolutionary Distribution of O-linked N-Acetylglucosamine
- Molecular Mimicry of Animal Glycans by Pathogens
- Interspecies and Intraspecies Differences in Glycosylation
- Why Do Widely Expressed Glycosyltransferases Have Limited Endogenous Functions?
- Future Directions
- References
- Chapter 4. Protein-Glycan Interactions
- Historical Background
- Recognition of Glycans by Proteins
- The “Water Problem”
- Atomic Details of Cholera Toxin Binding to the Pentasaccharide from GM1
- Kinetics of Glycan-Protein Interactions
- Biophysical Methods: X-ray and NMR
- Equilibrium Dialysis
- Affinity Chromatography
- Titration Calorimetry
- Surface Plasmon Resonance
- ELISA-type Assays
- IC50-Hapten Inhibition
- Precipitation
- Electrophoresis
- Expression of cDNAs for Ligands and Receptors
- Future Directions
- References
- Chapter 5. Exploring the Biological Roles of Glycans
- General Principles and Conclusions about Biological Roles of Glycans
- Biological Consequences of Altering Glycosylation Are Variable
- Structural and Modulatory Roles of Glycans
- Glycans as Specific Ligands for Exogenous Receptors
- Glycans as Specific Ligands for Endogenous Receptors
- The Same Glycan Can Have Different Roles within An Organism
- Are There “Junk” Glycans?
- Intraspecies and Interspecies Variations in Glycosylation
- Importance of Terminal Sequences, Modifications, and Unusual Structures
- Approaches to Uncovering Specific Biological Roles of Glycans
- Future Directions
- References
- Chapter 1. Historical Background and Overview
- Biosynthesis, Metabolism, and Function
- Chapter 6. Monosaccharide Metabolism
- Chapter 7. N-Glycans
- Background
- Synthesis of the Dolichol Oligosaccharide Precursor
- Transfer of the Dolichol Oligosaccharide Precursor to Nascent Proteins
- Initial Steps in N-Glycan Processing and Control of Protein Folding
- N-Glycan Processing and Trafficking Involving Terminal Mannose Linkages
- The Diversification of N-Glycans
- The General Biology of N-Glycans
- Future Directions
- References
- Chapter 8. O-Glycans
- Background
- O-Glycans as Compared to Other Types of Serine and Threonine Glycosylation
- Predicting Sites of O-Glycosylation
- A Family of Polypeptide GalNAc Transferases
- O-Glycan Diversification in Vertebrates: Core Subtype Formation
- Less Common O-Glycan Core Subtypes
- O-Glycan Biosynthesis and T Antigen Formation
- Mucin Polypeptide Genes
- Physical and Structural Functions of O-Glycans
- O-Glycan Functions in Endogenous Lectin-Ligand Interactions
- Future Directions
- References
- Chapter 9. Glycosphingolipids
- Historical Background
- Defining Structures, Major Classes, and Nomenclature
- Isolation, Purification, and Analysis
- Biosynthesis
- Trafficking, Turnover, and Degradation
- Relationships to Other Sphingolipids
- Antibodies against Glycosphingolipids
- Biological Roles
- Natural and Induced Disorders in Biosynthesis
- Future Directions
- References
- Chapter 10. Glycophospholipid Anchors
- Historical Background of the Discovery of GPI Anchors
- Diversity of Proteins Anchored via GPIs
- GPI Anchor Structures
- GPI Anchor Biosynthesis
- Mutations in the GPI Anchor Biosynthetic Pathway
- Identification of GPI-anchored Proteins
- Putative Functions of GPI Anchors
- Future Prospects and Directions
- References
- Chapter 11. Proteoglycans and Glycosaminoglycans
- Historical Perspective
- Proteoglycans and Glycosaminoglycans Are Components of Extracellular Matrices and Cell Surfaces
- Proteoglycans Interact with a Variety of Ligands
- Proteoglycans Exhibit Great Structural Diversity
- Hyaluronan Is the Simplest Glycosaminoglycan
- Keratan Sulfate, a Sulfated Polylactosamine
- Heparan Sulfate and Chondroitin Sulfate Are Linked by Xylose to Serine
- Chondroitin Sulfate/Dermatan Sulfate Biosynthesis
- Heparin and Heparan Sulfate Biosynthesis
- The Difference between Heparin and Heparan Sulfate
- Proteoglycans Turn Over Continuously
- Genetic Studies of Proteoglycan Structure, Function, and Metabolism
- Future Prospects
- References
- Chapter 12. Other Classes of Golgi-derived Glycans
- Chapter 13. Nuclear and Cytoplasmic Glycosylation
- Chapter 14. The O-GlcNAc Modification
- Chapter 15. Sialic Acids
- Historical Background
- Diversity in the Structure and Linkage of Sialic Acids
- Nomenclature and Abbreviations
- Oligosialic and Polysialic Acids
- Tissue-specific and Molecule-specific Expression of Sialic Acid Linkages and Modifications
- Biosynthesis and Turnover of Sialic Acids
- Biosynthesis and Turnover of Sialic Acid Modifications
- Methods for Studying Sialic Acids: Diversity Can Be Missed
- Sialic-Acid-binding Lectins
- Functions and Uses of Sialic-Acid-binding Lectins
- Sialic Acid Modifications in Development and Malignancy
- Future Directions
- References
- Chapter 16. Structures Common to Different Types of Glycans
- Background
- Regulated Glycosylation of Constitutively Expressed Precursors to Terminal Chain Structures
- Type-2 Chains
- Type-1 Chains
- Polylactosamines
- β1–6GlcNAc Branching Structures
- The A, B, and H Blood Group Structures
- Lewis Blood Group Structures
- P Blood Group Structures
- The α1–3Gal Structure
- The Forssman Antigen
- Sulfated Terminal β-linked GalNAc Structures on Pituitary Glycoproteins
- Sialylated Terminal β-linked GalNAc Structures
- α2–3-sialylated Structures
- α2–6-sialylated Structures
- α2–8-sialylated Structures
- Sulfated Glycans: L-Selectin Ligands, HNK-1, and Keratan Sulfate
- Future Directions
- References
- Chapter 17. Glycosyltransferases
- Glycan Biosynthesis Is Primarily Mediated by Glycosyltransferases
- General Properties of Glycosyltransferase Reactions
- Sequential Actions of Glycosyltransferases
- Exceptions to the One-Linkage-One-Enzyme Paradigm
- Effects of the Underlying Polypeptide on Glycosyltransferase Action
- Molecular Cloning of Glycosyltransferase Genes
- Primary Sequence Relationships among Glycosyltransferases
- Golgi Glycosyltransferases Have a Shared Secondary Structure
- Proteolytic Cleavage and Secretion of Golgi Glycosyltransferases
- Glycosyltransferases Are Often Glycoproteins Themselves
- Retention of Glycosyltransferases in Golgi Subcompartments
- Regulation of Glycosyltransferase Gene Expression
- Future Directions
- References
- Chapter 18. Degradation and Turnover of Glycans
- Chapter 19. Glycosylation in “Model” Organisms
- Chapter 20. Glycobiology of Plant Cells
- The Polysaccharide-rich Cell Wall Is the ECM of the Plant Cell
- ECM Glycoproteins Have Hydroxyproline Residues O-glycosylated with Short Arabinosides
- Extracellular Arabinogalactan Proteins Are Markers for Cell Fate and Can Induce Embryogenesis
- Growth of the Plant Cell Requires Loosening of the Xyloglucan Network, a Process Mediated by Proteins and Oligosaccharides
- The ECM Is a Source of Oligosaccharide Signals for Defense against Pathogens
- Glycolipid Signals Have a Key Role in Establishing a Symbiotic Relationship between Nitrogen-fixing Bacteria and Plants
- Complex N-Glycans on Plant Glycoproteins Differ from Those on Mammalian and Yeast Glycoproteins and Can Be Highly Immunogenic
- Production of Mammalian Glycoproteins in Plants Requires the Use of Mutant Plants That Synthesize Different N-linked Glycans
- Lectins Are Involved in Recognition of Pathogens, Pests, and Symbionts
- Future Directions
- References
- Chapter 21. Bacterial Polysaccharides
- Proteins That Recognize Glycans
- Chapter 22. Discovery and Classification of Animal Lectins
- Historical Background of the Discovery of Animal Lectins
- Current Classification of Animal Lectins
- Biosynthesis, Trafficking, and Regulation of Animal Lectins
- Soluble and Membrane-bound Forms of Animal Lectins
- Nature of Lectin-Ligand Interactions
- Animal Lectins Are Generally Multivalent
- Nature of the Ligands for Animal Lectins
- Types of Functions Mediated by Animal Lectins
- Future Directions
- References
- Chapter 23. P-type Lectins
- I-Cell Disease and the “Common Recognition Marker” of Lysosomal Enzymes
- Discovery of the Phosphomannosyl Recognition Marker
- Enzymatic Mechanism for Generation of the Recognition Marker
- Enzymatic Basis for I-Cell Disease and Pseudo-Hurler Polydystrophy
- Variants of I-Cell Disease and Pseudo-Hurler Polydystrophy
- Recognition of Lysosomal Enzymes by the Phosphotransferase
- Man-6-P Receptors
- The Cation-independent Receptor Binds to Other Ligands
- Consequences of Natural and Induced Genetic Defects in the MPRs
- Relative Roles of the Two MPRs in Lysosomal Enzyme Trafficking
- Mechanisms of Subcellular Trafficking of the Two MPRs
- Evolutionary Origins of the MPR System
- Alternate Pathways for the Trafficking of Lysosomal Enzymes
- Significance of Man-6-P on Nonlysosomal Proteins
- Future Directions
- References
- Chapter 24. I-type Lectins
- Chapter 25. C-type Lectins
- Historical Background and Discovery of C-type Lectins
- Definition of the C-type Lectins and Sequence Motifs
- Different Subfamilies of C-type Lectins
- The Collectins
- The Selectins
- The Lymphocyte Lectins
- The Proteoglycans
- Other Types of C-type Lectins
- Tertiary/Quaternary Structures of C-type Lectins
- Future Directions
- References
- Chapter 26. Selectins
- Background
- L-Selectin Structure and Expression
- L-Selectin Ligands on High Endothelial Venules
- L-Selectin-dependent Leukocyte Adhesion to Microvascular Endothelium
- E-Selectin Structure and Regulation
- E-Selectin Ligands
- P-Selectin Structure and Expression
- P-Selectin Ligands
- Glycosyltransferases Involved in Selectin Ligand Biosynthesis
- Future Directions
- References
- Chapter 27. S-type Lectins (Galectins)
- Chapter 28. Microbial Carbohydrate-binding Proteins
- Introduction
- Methods for Studying Microbial Binding and Adhesion
- Microbial Adhesins and Cell Surface Glycoconjugate Receptors
- Adhesins That Bind to Glycolipids
- Adhesins That Bind to Glycoproteins
- Adhesins That Bind to Glycosaminoglycans
- Microbial Carbohydrate Ligands for Animal Cell Lectins
- Future Directions
- References
- Chapter 29. Glycosaminoglycan-binding Proteins
- Introduction
- Many Glycosaminoglycan-binding Proteins Occur in Nature
- Methods for Measuring Gag-Protein Binding
- Conformational and Sequence Considerations
- Do Consensus Sequences Exist in Gag-binding Proteins?
- Antithrombin-Heparin: A Paradigm for Studying GAG-binding Proteins
- FGF-Heparin Interactions Enhance Stimulation of FGF-Receptor Signal Transduction
- Hyaluronan-Protein Interactions
- Other Gag-Protein Interactions
- Future Directions
- References
- Chapter 30. Plant Lectins
- Chapter 22. Discovery and Classification of Animal Lectins
- Glycans in Genetic Disorders and Disease
- Chapter 31. Genetic Disorders of Glycosylation in Cultured Cells
- Chapter 32. Naturally Occurring Genetic Disorders of Glycosylation
- Introduction
- Spontaneous Mutations in Humans and Animal Models
- Clinical and Laboratory Features of the CDGSs
- CDGS Type Ia
- CDGS Type Ib
- CDGS Type Ic
- CDGS Type II
- CDGS Types III and IV
- Leukocyte Adhesion Deficiency II Syndrome
- Congenital Dyserythropoietic Anemia Type II
- Galactosemia
- Defects in Proteoglycan Synthesis
- Future Directions
- References
- Chapter 33. Determining Glycan Function Using Genetically Modified Mice
- Chapter 34. Glycosylation Changes in Ontogeny and Cell Activation
- Chapter 35. Glycosylation Changes in Cancer
- Historical Background
- Ways in Which Glycosylation Can Be Altered in Malignant Cells
- Altered Branching of N-Glycans
- Changes in the Amount, Linkage, and Acetylation of Sialic Acids
- Expression of N-Glycolylneuraminic Acid in Human Tumors
- Alterations in Glycosaminoglycan Expression
- Pathological Roles of Mucins with Altered Glycosylation
- Sialylated Lewis Structures and Selectin Ligands on Cancer Cells
- Altered Expression and Shedding of Glycosphingolipids
- Galectins and Polylactosamine Expression
- Altered Expression of the ABH(O) Blood-Group-related Structures
- Loss of Glycophospholipid Anchor Expression
- Practical Significance of Altered Glycosylation in Tumor Cells
- Future Directions
- References
- Chapter 36. Glycobiology of Protozoal and Helminthic Parasites
- Chapter 37. Acquired Glycosylation Changes in Human Disease
- Cardiovascular Medicine
- Dermatology: Role of Selectins in Inflammatory Skin Diseases
- Endocrinology and Metabolism: Altered Glycosylation and the Complications of Diabetes Mellitus
- Gastroenterology
- Hematology
- Immunology and Rheumatology
- Infectious Disease
- Nephrology
- Neurology and Psychiatry
- Oncology: Altered Glycosylation in Cancer
- Pulmonary Medicine
- Future Directions
- References
- Methods and Applications
- Chapter 38. Principles of Structural Analysis and Sequencing of Glycans
- Chapter 39. Chemical and Enzymatic Synthesis of Glycans
- Background
- Oligosaccharide Synthesis Is More Difficult Than DNA or Peptide Synthesis
- Complexities and Challenges in the Chemical Synthesis of Oligosaccharides
- A Representative Trisaccharide Synthesis
- Enzymatic Synthesis of Oligosaccharides
- Synthesis of Oligosaccharides Catalyzed by Glycosidases
- Synthesis of Oligosaccharides Using Glycosyltransferases
- Future Prospects
- References
- Chapter 40. Natural and Synthetic Inhibitors of Glycosylation
- Introduction
- Indirect Inhibitors and Metabolic Poisons
- Tunicamycin: Inhibition of DOL-PP-GlcNAc Assembly
- Plant Alkaloids: Natural Inhibitors of Glycosidases
- Substrate Analogs: Directed Synthesis of Inhibitors
- Glycoside Primers: Mimicking What Already Works
- Inhibitors of Glycolipids and GPI Anchors
- Neuraminidase Inhibitors: Rational Design from X-ray Crystal Structures
- Future Directions
- References
- Chapter 41. Glycobiology in Biotechnology and Medicine
- Glossary: Commonly Used Terms
- Essentials of GlycobiologyEssentials of Glycobiology
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