Cell Surface Receptors (eBook)

Cover 1
Contents 6
Preface 12
Chapter 1. Structure and Function of the Epidermal Growth Factor (EGF/ErbB) Family of Receptors 14
I. Introduction 14
II. The EGF and EGFR Families 16
III. Association of ErbB Receptors with Human Disease 19
IV. Structure of Individual ErbB Receptor Domains 20
V. Structure of Entire ErbB Receptor Ectodomains 22
VI. HER2 28
VII. Therapeutic Anti-HER2 Antibodies 31
VIII. Remaining Questions 33
References 35
Chapter 2. The Three-Dimensional Structure of Integrins and Their Ligands, and Conformational Regulation of Cell Adhesion 42
I. Introduction 43
II. Conformational Regulation of Integrin Structure and Function 44
III. Integrin/Ligand Interactions 60
References 70
Chapter 3. Structures of Axon Guidance Molecules and Their Neuronal Receptors 78
I. Introduction 78
II. Eph Receptors and Ephrins 79
III. Semaphorins, Neuropilins, and Plexins 95
IV. Myelin-Associated Inhibitors of Axonal Regeneration 103
V. Conclusion and Perspectives 111
References 112
Chapter 4. Shared Cytokine Signaling Receptors: Structural Insights from the gp130 System 120
I. Cross-Reactive Signaling Receptors in Biology 121
II. Cytokines and Receptors 122
III. The Growth Hormone Paradigm: Generalities and Limitations 123
IV. Shared Signaling Receptors for Hematopoietic Cytokines 126
V. gp130 Family of Cytokines and Receptors 131
VI. A Structural Basis of gp130 Cross Reactivity: Site II 141
VII. Thermodynamic Basis for a Universal Binding Solution 143
VIII. Cross-Reactivity of the gp130 IGD with Cytokine Site III 145
IX. Predicting the Higher-Order Assemblies of the Asymmetric Complexes (gp130/LIFR) 148
X. Translating Ligand Recognition into Signaling 150
References 152
Chapter 5. The Structural Basis for Biological Signaling, Regulation, and Specificity in the Growth Hormone–Prolactin System of Hormones and Receptors 160
I. Structural Basis for Receptor Homodimerization 162
II. Hormone Receptor Binding Sites 165
III. Hormone-Receptor Binding Energetics: The Binding ‘‘Hot-Spot’’ Concept 168
IV. Stereoselectivity of the Prolactin Receptor (hPRLR) 171
V. Comparison of the hGH Site1 and Site2 Binding Energy Epitopes in the hGH-hGHR Ternary Complex 172
VI. Protein Engineering to Create New Properties 173
VII. Allosteric Effects, A Big Surprise 174
VIII. Biological Implications of Transient Receptor Dimerization 177
IX. Mechanism of ECD2 Binding, the Regulation Step in Biological Signaling 178
X. Future Directions 178
References 179
Chapter 6. Structural Analysis of IL-10 and Type I Interferon Family Members and Their Complexes with Receptor 184
I. Introduction 184
II. Structures of the HCIIs 190
III. Structures of the Class 2 Homology Region (C2HR) 208
IV. Structure of the High-Affinity HCII/C2HR Interfaces 217
V. Concluding Remarks 228
References 228
Chapter 7. Assembly of Post-Receptor Singnaling Complexes for the Tumor Necrosis Factor Receptor Superfamily 238
I. Introduction 239
II. Domain and Oligomeric Structures of TRAFs 247
III. TRAF2-Receptor Interactions: Establishment of the Paradigm 254
IV. TRAF3-Receptor Interactions: Similarities and Differences with TRAF2 261
V. TRAF6-Receptor Interactions: Distinct Specificity 264
VI. Thermodynamics of TRAF-Receptor Interactions 267
VII. TRAF2-TRADD Interaction: A Novel Mode of TRAF Signaling 269
VIII. TRAF Signaling Inhibitors 274
IX. DD and DD-DD Interactions 275
X. Conclusion: Emerging Principles of Post-Receptor Signal Transduction 278
References 284
Chapter 8. NKG2D and Related Immunoreceptors 294
I. T Cell Receptors and MHC Class I Proteins: Paradigms of Immunological Recognition 295
II. NK Cells and Receptors 297
III. NKG2x NK Cell Receptors 301
IV. HuNKG2D Ligands: MIC-A/B 304
V. HuNKG2D Ligands: ULBPs 306
VI. MuNKG2D Ligands: RAE-1s, H60, and MULT1 307
VII. NKG2D–Ligand Complexation 308
VIII. NKG2D–Ligand Recognition Degeneracy: ‘‘Rigid Adaptation’’ Rather Than ‘‘Induced-Fit’’ 312
IX. NKG2D: Open Questions 316
X. NKG2D: Implications for NKG2x–CD94 Recognition 317
XI. MIC and yd TCRs 319
References 320
Chapter 9. Ionotropic Glutamate Receptor Recognition and Activation 326
I. Introduction 327
II. Beginnings of Structure: Cloning, Mutagenesis, Transmembrane Topology, and Homology Models 328
III. The Amino Terminal Domain (ATD) 331
IV. Structure and Dynamics of the Glutamate-Binding Domain 332
V. Structure of the Ion Channel 342
VI. The C-Terminal Domain 344
VII. Relating Structure, Function, and Dynamics: Channel Gating and Desensitization 345
VIII. Evolution of Glutamate Receptors 352
IX. Summary 354
References 354
Chapter 10. Chemokine-Receptor Interactions: GPCRs, Glycosaminoglycans and Viral Chemokine Binding Proteins 364
I. Introduction 365
II. The Chemokine Superfamily 367
III. Interaction of Chemokines and Glycosaminoglycans 380
IV. Viral Chemokines and Receptors, Chemokine Mimics, and Chemokine Binding Proteins 386
V. Chemokines and Disease 391
References 394
Chapter 11. Chemotaxis Receptors and Signaling 406
I. Introduction to Chemotaxis 407
II. Signal Transduction Events 409
III. G Protein-Coupled Receptors 413
IV. Conserved Elements of GPCR Structure 415
V. Rhodopsin Structure 420
VI. Proposed GPCR Activation Mechanisms 421
VII. Activation Mechanisms of Specific Chemotaxis GPCRs 426
VIII. Receptor Oligomerization 439
IX. Conclusions 442
References 445
Author Index 458
Subject Index 500
Color Plate Section 520