Main description:

In the last decade there has been a great expansion in our knowledge of the existence, nature and functions of mammalian carbohydrate binding proteins. This book covers the structures and postulated functions for the major classes of mammalian carbohydrate binding proteins. These include intracellular lectins involved in diverse functions such as protein synthesis quality control, targetting of lysosomal enzymes and in the secretory pathway. In addition, several chapters are devoted to other major families of lectins that are found at the cell surface or in extracellular fluids which are involved in various recognition functions such as cell-cell interactions in inflammation and recognition of pathogen carbohydrates in host defence.

Contents:

Lectins of the ER Quality Control Machinery.- 1 Introduction.- 2 Structural Aspects.- 3 Calnexin and Calreticulin in Quality Control of Glycoprotein Folding.- 4 Calnexin and Calreticulin in Glycoprotein Degradation.- 5 Regulation of Calnexin/Calreticulin-Substrate Interaction.- 5.1 Modifications of the Luminal Domain.- 5.2 Alterations of the Cytosolic Tail.- 6 Conclusions.- References.- MR60/ERGIC-53, a Mannose-Specific Shuttling Intracellular Membrane Lectin.- 1 Discovery.- 2 Structural Features.- 3 Intracellular Mannose-Specific Animal Lectins Are Homologous to Leguminous Plant Lectins.- 4 Oligomerization and Sugar Binding Activity.- 5 Cytological Features.- 6 Deciphering the Role of MR60/ERGIC-53: Looking for Highly Specific Oligosaccharide and Natural Glycoprotein Ligands.- 7 Concluding Remarks.- References.- The Cation-Dependent Mannose 6-Phosphate Receptor.- 1 Introduction.- 2 Intracellular Trafficking of the MPRs and Lysosomal Enzymes.- 2.1 Generation of the Mannose 6-Phosphate Recognition Marker.- 2.2 Subcellular Distribution of the MPRs.- 2.3 Targeting Signals in the Cytoplasmic Region of the MPRs.- 3 Primary Structure and Biosynthesis of the CD-MPR.- 3.1 Primary Structure.- 3.2 Genomic Structure.- 3.3 Oligomeric Structure.- 3.4 Co- and Post-Translational Modifications.- 3.4.1 Acylation.- 3.4.2 Phosphorylation.- 3.4.3 Glycosylation.- 4 Carbohydrate Recognition by the CD-MPR.- 4.1 Lysosomal Enzyme Recognition.- 4.2 Expression of Mutant Forms of the CD-MPR.- 4.3 Crystal Structure of the CD-MPR in the Presence of Bound Man-6-P.- 4.3.1 Polypeptide Fold.- 4.3.2 Structural Similarity to Biotin-Binding Proteins.- 4.3.3 Dimeric Structure.- 4.3.4 Carbohydrate Binding Pocket.- 4.3.5 Comparison of the CRDs of the CD-MPR and CI-MPR.- 5 Concluding Remarks.- References.- Galectins Structure and Function - A Synopsis.- 1 Introduction.- 1.1 Discovery of Galectins - Past and Present.- 2 Structure, Specificity, and Endogenous Ligands.- 2.1 The Carbohydrate Recognition Domain (CRD) and Carbohydrate Binding Site.- 2.2 Domain Organization, Oligomerization, and Valency.- 2.3 Endogenous Galectin Glycoconjugate Ligands.- 3 Genes, Expression, and Targeting.- 3.1 Galectin Genes.- 3.2 Galectin Distribution in Cells and Tissues.- 3.3 Synthesis, Intracellular Targeting and Secretion.- 4 Functional Effects.- 4.1 Cell Adhesion.- 4.2 Galectin Induced Signaling.- 4.3 Galectins in Apoptosis.- 4.4 Galectins and Galectin Inhibitors In Vivo.- 4.5 Nuclear Functions.- 4.6 Other Galectin Effects.- 4.7 Galectin Null-Mutant Mice.- 5 Biological Roles and Biomedical Use.- 5.1 Immunity and Inflammation.- 5.2 Host-Pathogen Interaction.- 5.3 Cancer.- 5.4 Galectin Serology.- 5.5 Tissue Organization and Repair.- 5.6 Galectins in the Nervous System.- 6 Summary and Conclusions.- References.- Structure and Function of CD44: Characteristic Molecular Features and Analysis of the Hyaluronan Binding Site.- 1 Synopsis.- 2 Cell Adhesion Proteins.- 2.1 Representative Families and Characteristic Features.- 3 Molecular Structure of CD44.- 3.1 Cloning of CD44 and Domain Organization.- 3.2 Genomic Structure and Isoforms.- 3.3 Glycosylation.- 4 Biological Functions and Ligands of CD44.- 4.1 Functional Diversity.- 4.2 Hyaluronan and Other Ligands.- 4.3 Regulation of Hyaluronan Binding.- 4.4 Hyaluronan Binding Domain.- 5 The Link Protein Module.- 5.1 Three-Dimensional Structure of TSG-6.- 5.2 Molecular Model of the Link Module of CD44.- 6 Analysis of the Hyaluronan Binding Site in CD44.- 6.1 Mutagenesis Strategy and Experimental Approach.- 6.2 Classification of Targeted Residues.- 6.3 Mapping and Characterization of the Binding Site.- 6.4 Opportunities and Limitations.- 7 Comparison of Carbohydrate Binding Sites.- 7.1 Link Proteins and C-Type Lectins.- 8 Conclusions.- References.- Structure and Function of the Macrophage Mannose Receptor.- 1 Functions and Biological Ligands of the Mannose Receptor.- 1.1 Identification and Localization of the Mannose Receptor.- 1.2 Roles of the Mannose Receptor in the Immune Response.- 1.3 Clearance of Soluble Endogenous Ligands by the Mannose Receptor.- 2 Structure of the Mannose Receptor.- 2.1 Primary Structure.- 2.2 Features of Individual Domains.- 2.2.1 The Cytoplasmic Tail.- 2.2.2 The N-Terminal Cysteine-Rich Domain and the Fibronectin Type II Repeat.- 2.2.3 The C-Type Carbohydrate Recognition Domains.- 3 Mechanisms of Carbohydrate Binding by the Mannose Receptor.- 3.1 Roles of Individual Domains.- 3.2 Molecular Mechanism of Monosaccharide Binding to the Fourth Carbohydrate-Recognition Domain.- 3.2.1 Interaction of Ca2+ with CRD-4.- 3.2.2 Involvement of a Stacking Interaction in Sugar Binding to CRD-4.- 3.2.3 Determinants of Specificity and Orientation of Monosaccharides Bound to CRD-4.- 3.3 Spatial Arrangement of Domains.- 4 The Mannose Receptor Family.- 4.1 Members of the Family.- 4.2 Ligand Binding by Members of the Mannose Receptor Family.- 4.3 Evolution of the Mannose Receptor Family.- 5 Conclusions.- References.- The Man/GalNAc-4-SO4-Receptor has Multiple Specificities and Functions.- 1 Introduction.- 2 Oligosaccharides Terminating with the Sequence SO4-4GalNAc?1,4GlcNAc?1,2Man? (S4GGnM) Are Found on the Pituitary Glycoprotein Hormones of All Vertebrates.- 3 Terminal ?1,4-Linked GalNAc-4-SO4 Determines the Circulatory Half-life of LH.- 4 The Ga1NAc-4-SO4-Receptor: A Receptor with Multiple Carbohydrate Specificities and Functions.- 5 Functional Significance of the Man/Ga1NAc-4-SO4-Receptor.- 6 Future Directions.- References.- Sialoadhesin Structure.- 1 Introduction.- 2 Sialoadhesin Carbohydrate-Binding Domain Structure and Function.- 3 Comparison with Other Sialic Acid-Binding Proteins.- 4 Sialic Acid Mediated Cell Adhesion.- 5 Conclusion.- References.- Ligands for Siglecs.- 1 Introduction.- 1.1 Sialic Acids in Cell Recognition.- 1.2 Selectins.- 1.3 Siglecs.- 2 Structures of Siglecs.- 2.1 Sialic Acid-Binding Domain.- 2.1 Glycosylation.- 3 Carbohydrate Recognition.- 3.1 Methodology.- 3.1.1 Cell Surface Resialylation and Neoglycoconjugates.- 3.1.2 Cell Binding Assays.- 3.1.3 Fc-Chimeras.- 3.2 Sialic Acid Interactions with Siglecs.- 3.2.1 Functional Groups of Sialic Acids and Amino Acids.- 3.3 Glycan Interactions with Siglecs.- 3.3.1 Linkage Specificity.- 3.4 Ligands.- 3.4.1 Cell Surface Glycoproteins.- 3.4.2 Extracellular Glycoproteins.- 3.4.3 Glycolipids.- 3.5 Potential Regulation by cis-Interactions or Soluble Competitors.- 4 Perspectives.- References.- Functions of Selectins.- 1 Selectin Structure and Expression.- 1.1 Selectin Structure.- 1.2 Expression of E-selectin.- 1.3 Expression of P-selectin.- 1.4 Expression of L-selectin.- 2 Functions Common to All Selectins.- 2.1 Adhesion Under Flow.- 2.2 Leukocyte Adhesion Cascade.- 2.3 Selectin Bond Mechanics.- 3 Differential Functions of Selectins.- 3.1 P-selectin.- 3.2 E-selectin.- 3.3 L-selectin.- 3.4 Homing of Bone Marrow Stem Cells.- 4 Signaling through Selectins.- 5 Selectin Ligands.- 5.1 PSGL-1.- 5.2 Other Selectin Ligands.- 6 Phenotype of Selectin-Deficient Mice.- 6.1 E- and P-Selectin Double Deficient Mice.- 6.2 Triple Selectin Deficient Mice.- 6.3 L-Selectin-Deficient Mice.- 6.4 P-Selectin Deficient Mice.- 6.5 E-Selectin-Deficient Mice.- 6.6 L- and E- and L- and P-Selectin Double Deficient Mice.- 7 Selectin Ligand Deficiencies.- 7.1 Selectin Ligand Deficiencies in Mice.- 7.2 Selectin Ligand Deficiency in Humans.- 8 Selectins and Disease.- 8.1 Ischemia and Reperfusion.- 8.2 Cancer Metastasis.- 8.3 Autoimmune Diseases.- 8.4 Atherosclerosis.- 9 Summary.- References.- Carbohydrate Ligands for the Leukocyte-Endothelium Adhesion Molecules, Selectins.- 1 Introduction.- 2 Carbohydrate Ligands for E-Selectin.- 2.1 The Initial Evaluations of the Lex and Lea Systems as Ligands.- 2.2 The Search for Epithelial and Myeloid Cell Ligands.- 2.3 Conclusions and Questions Regarding the Carbohydrate Sequences Recognized by E-Selectin.- 3 Carbohydrate Ligands for L-Selectin.- 3.1 Initial Explorations of Carbohydrate Sequences Recognized by L-Selectin.- 3.2 Novel Sulfated Sequences Detected on the Endothelial Glycoprotein GIyCAM-1.- 3.3 Chemically Synthesized Sulfated Forms of the Lex Pentasaccharide, and Their Interactions with L-Selectin.- 3.4 Clues to the Existence of Novel Biosynthetic Pathways for Selectin Ligands.- 3.5 The Second Class of Sulfated L-Selectin Ligand.- 3.6 Possible Co-Operativity Between the Long and Short Ligands for L-Selectin.- 4 Oligosaccharide Ligands for P-Selectin.- 4.1 P-selectin Interactions with Defined Saccharide Sequences.- 4.2 PSGL-1, the Counter-Receptor Displaying Two Classes of Ligand for P-Selectin.- 5 Perspectives.- References.- Structures and Functions of Mammalian Collectins.- 1 Introduction.- 2 Mannose-Binding Lectin (MBL).- 2.1 Molecular Structure and Assembly of MBL.- 2.2 Biological Functions of MBL.- 2.3 Interaction of MBL with Micro-organisms.- 2.4 Gene Organisation and Genetics of MBL.- 2.5 Crystal Structure of Trimeric CRDs of MBL.- 3 Surfactant Protein A (SP-A).- 3.1 SP-A Suprastructure and Assembly.- 3.2 SP-A Gene and Genomic Organisation.- 3.3 SP-A-Carbohydrate Interaction.- 3.4 SP-A-Phospholipid Interactions.- 3.5 SP-A-Type II Cell Interaction.- 3.6 Interaction of SP-A with Phagocytes.- 3.7 Interaction of SP-A with Pathogens and Allergens.- 4 Surfactant Protein D (SP-D).- 4.1 Molecular Structure and Assembly of SP-D.- 4.2 Interaction of SP-D with Carbohydrate and Lipid Ligands.- 4.3 Interaction of SP-D with Pathogens and Allergens.- 4.4 SP-D Gene Organisation and Genetics.- 4.5 SP-D Crystal Structure.- 5 Cell Surface Receptors for Collectins.- 6 SP-A and SP-D Gene Knock-out Mice.- 7 SP-A and SP-D in Human Diseases.- 8 Bovine Collectins: Conglutinin (BC) and Collectin-43 (CL-43).- References.