Hormone Receptors: Structures and Functions

Name: Hormone Receptors: Structures and Functions
Brand: Academic Press
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Gerald Litwack(Herausgeber*in)

Academic Press

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Erschienen am 15. September 2023

300 Seiten

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Intro
Hormone Receptors: Structures and Functions
Copyright
Former Editors
Contents
Contributors
About the editor
Preface
Chapter One: Signaling mechanism of growth hormone-releasing hormone receptor
1. Overview of growth hormone-releasing hormone (GHRH) and GHRH receptors (GHRH-R)
1.1. G-protein-coupled receptors
1.2. Structure of GHRH-R
1.3. Conformational changes in structure of GPCRs including the GHRH-R
1.4. The presence of GHRH-R in human tissues
1.5. Splicing and splice variants of GHRH-R
1.6. Expression and signaling of SV1 of GHRH-R in different tissues
2. Signaling mechanism and regulation of GHRH-R
2.1. Signaling in lipopolysaccharide (LPS)-induced acute ocular inflammation
2.2. Mechanism of hormone binding by the GHRH-R
2.3. Factors effecting binding of GHRH to GHRH-R
3. Expression and regulation of GHRH-R and the role of GHRH agonists and antagonists in diseases and therapy
Acknowledgments
References
Chapter Two: Unraveling corticotropin-releasing factor family-orchestrated signaling and function in both sexes
1. Overview of the CRF family
1.1. Studying biology of sex differences
1.2. Two arms of stress response: Initiation and recovery
2. Transcriptional regulation of CRF system
2.1. Transcriptional regulation of CRF and Urocortins by nuclear and steroid receptors
2.2. Transcriptional regulation of CRHR1
2.3. Transcriptional regulation of CRHR2
3. The CRF receptors
3.1. Signal transduction by CRF receptors
3.2. CRF receptor heteromerization and altered signaling
3.3. Cell cytoskeleton in GPCR signaling
4. Sex differences mediated by CRF2 in the periphery
4.1. Sex differences in pancreatic diseases
4.1.1. Sex-differences in pancreatitis histopathology
4.1.2. Sex differences in endoplasmic reticulum ultrastructure and unfolded protein response
4.2. CRF2 and kinase crosstalk
4.3. Sex differences in diabetes: Role of Urocortins and CRF2
5. Conclusions and future directions
Acknowledgments
References
Chapter Three: Structures of the arginine-vasopressin and oxytocin receptor signaling complexes
1. Arginine-vasopressin and oxytocin receptors, biological functions and therapeutic value
2. Antagonist-bound OT receptor structure
3. Hormone-bound G protein-coupled V2 and OT receptor signaling complexes
4. Hormone-bound ß-arrestin1-coupled V2 receptor signaling complex
5. Conserved AVP/OT binding site in the receptor family
6. Molecular mechanisms of V2R/OTR activation
7. Gs/Gq coupling interface in V2/OT receptors
8. Gs/ßarrestin1 coupling interface in V2 receptor
9. Future perspectives: From structure to clinic
Acknowledgments
References
Chapter Four: Growth hormone receptor gene disruption
1. Introduction
2. GHRKO mice
2.1. Background
2.2. Phenotype
3. Inducible GHRKO mice
3.1. Background
3.2. Phenotype
4. Liver-specific GHRKO mice
4.1. Background
4.2. Phenotype
5. Muscle GHRKO mice
5.1. Background
5.2. Phenotype
6. Adipose tissue GHRKO mice
6.1. Background
6.2. Phenotype
7. Disruption of GHR in brain or specific neurons
7.1. Background
7.2. Phenotype
8. Macrophage-specific GHRKO
8.1. Background
8.2. Phenotype
9. Hematopoietic stem cell GHRKO mice
9.1. Background
9.2. Phenotype
10. Intestine-specific GHRKO
10.1. Background
10.2. Phenotype
11. ß cell-specific GHRKO
11.1. Background
11.2. Phenotype
12. Bone-specific GHRKO
12.1. Background
12.2. Phenotype
13. Heart-specific GHRKO mice
13.1. Background
13.2. Phenotype
14. Concluding remarks
References
Chapter Five: The three-dimensional structure of insulin and its receptor
1. General introduction
1.1. Biological action of insulin
2. Structure of insulin
2.1. Overall biophysical and biochemical properties
2.2. Defining the insulin residues involved in IR binding
3. Structure of the insulin receptor
3.1. Overall biophysical and biochemical properties
3.1.1. Domain arrangement
3.1.2. Insulin binding and negative cooperativity
3.1.3. Tyrosine kinase activation and signaling
3.2. Mechanisms of insulin binding and IR activation revealed by structural studies
3.3. Signaling bias at the IR
4. Concluding remarks
Acknowledgments
References
Chapter Six: Mutations at hypothetical binding site 2 in insulin and insulin-like growth factors 1 and 2
1. Introduction
2. Crystal and nuclear magnetic resonance (NMR) structures of insulin
3. Crystal and NMR structures of IGF-1 and IGF-2
4. Localization of binding site 1 in insulin
5. Kinetic studies and the first evidence for the existence of site 2 in insulin
5.1. Negative cooperativity of the IR and the first evidence for the existence of more than one binding site for a hormon ...
5.2. Binding of IGF-1 to IGF-1R and negative cooperativity of IGF-1R
5.3. First models for insulin:IR interactions
5.4. The first crystal structure of the apo IR ectodomain and the harmonic oscillator model
6. Mutagenesis of hypothetical site 2 residues in insulin and in IGF-1 and IGF-2
6.1. Positions in insulin predicted to be part of binding site 2 for IR
6.2. Positions in IGF-1 and IGF-2 predicted to be part of binding site 1 and site 2 for IGF-1R
6.3. ThrA8 in insulin, Phe49 in IGF-1 and Phe48 IGF-2
6.4. IleA10 in insulin, Ser51 in IGF1-1 and Ser50 in IGF-2
6.5. SerA12 in insulin, Asp53 in IGF-1 and Asp52 in IGF-2
6.6. LeuA13 in insulin, Leu54 in IGF-1, Leu53 IGF-2
6.7. GluA17 in insulin, Glu58 in IGF-1 and Glu57 in IGF-2
6.8. HisB10 in insulin, Glu9 in IGF-1, Glu12 in IGF-2
6.9. GluB13 in insulin, Asp12 in IGF-1 and Asp15 in IGF-2
6.10. LeuB17 in insulin, Phe16 in IGF-1 and Phe19 in IGF-2
7. Localization of site 2 residues based on cryoEM structures of hormone: Receptor complexes
8. Correlation of cryoEM structures with site 2 mutagenesis results in insulin
9. Correlation of cryoEM structures with site 2 mutagenesis results in IGF-1
10. Correlation of cryoEM structures with site 2 mutagenesis results in IGF-2
10.1. Concluding remarks
Acknowledgments
References
Chapter Seven: A structural perspective of liver X receptors
1. Introduction
2. Structural features of DBD domain
3. Structural features of LBD domain
4. Multi-domain structure
5. The N-terminal domain
References
Chapter Eight: Hepcidin and its multiple partners: Complex regulation of iron metabolism in health and disease
1. Introduction
2. Regulation of iron metabolism
2.1. Systemic iron metabolism regulation
2.2. Cellular regulation of iron metabolism
3. Physiological regulation of hepcidin expression
4. Hepcidin regulation by inflammation
5. Hepcidin regulation by erythropoiesis
6. Hepcidin regulation and hepcidin-independent regulation of iron absorption by hypoxia
7. Hepcidin-ferroportin axis regulates iron flows
8. Hepcidin-ferroportin axis in disease
8.1. Hereditary hemochromatosis
8.2. Iron-loading anemias
8.3. Anemia of chronic inflammation
8.4. Polycythemia vera
9. Targeting the hepcidin:ferroportin axis for therapeutic purposes
10. Conclusion
References
Chapter Nine: Structure-function relationships of the aldosterone receptor
1. Nuclear receptor superfamily
1.1. The mineralocorticoid receptor (MR)
1.2. 11ß-Hydroxysteroid dehydrogenase type 2 (11ß-HSD2)
2. Structural characterization of the MR
2.1. The N-terminal domain (NTD)
2.2. The MR N/C-interaction
3. The MR DNA-binding domain (DBD)
3.1. Mineralocorticoid response elements
3.2. HRE-independent interactions
3.3. The MR hinge region
4. The ligand-binding domain (LBD)
4.1. Specificity of MR ligand binding
4.2. Agonism at the MR
4.3. Phosphorylation of the MR LBD
4.4. Antagonism at the MR
4.5. Progesterone and the MR
4.6. Homodimerization of the MR
4.7. Heterodimerization of the MR
4.8. Non-steroidal antagonists and modulators of the MR
5. Coactivators and corepressors
5.1. MR-specific coregulators
6. Conclusions and future directions
Acknowledgments
Conflict of interest statement
References
Chapter Ten: Genomically anchored vitamin D receptor mediates an abundance of bioprotective actions elicited by its 1,25- ...
1. Introduction
1.1. Background on the vitamin D receptor (VDR)
1.1.1. Early history of VDR
1.1.2. Molecular anatomy of VDR
1.1.3. Biochemical mechanism of 1,25-dihyroxyvitamin D (1,25D)/VDR action
1.2. Kidney is the endocrine source of 1,25D, the physiologic ligand for the VDR
1.2.1. Calcium homeostasis endocrine loop
1.2.2. Phosphate homeostasis endocrine loop
1.2.3. Bone mineral endocrine physiology
1.2.4. Renal autocrine effects of 1,25D/VDR
2. Biologic actions of the 1,25-dihydroxyvitamin D hormone receptor
2.1. Endocrine actions of 1,25D/VDR
2.1.1. Direct influences on bone
2.1.2. Intestinal calcium absorption and barrier function maintenance
2.1.3. Parathyroid and endocrine pancreas influences
2.1.3.1. Parathyroid glands
2.1.3.2. Pancreatic ß cells
2.2. Intracrine activities of locally generated 1,25D via VDR binding
2.2.1. Immune system modulation (infection and immunity)
2.2.2. Nervous system manifestations
2.2.3. Autophagy, a novel systemwide activity of 1,25D/VDR impacting health
3. Closing comments
References
Chapter Eleven: Cryo-EM technique and its application: Structure of steroid hormone receptors
1. Introduction
2. General cryo-EM approaches and technology
3. Structure of steroid hormone receptors using cryo-EM
4. Summary and perspectives
References
Chapter Twelve: Structure and functions of the N-terminal domain of steroid hormone receptors
1. Introduction
2. The structure and functions of the SHRs
3. The structure and functions of the N-terminal domain (NTD) of the SHRs
4. The functional folding of the NTD/AF1 of the SHRs
5. Role of coregulatory proteins in the structure and functions of the SHRs´ NTD/AF1
6. Summary and future perspectives
References
Chapter Thirteen: The human glucocorticoid receptor
1. Introduction
2. Evolution of glucocorticoid receptor
3. The human glucocorticoid receptor (hGR)
4. Glucocorticoid signaling
5. NR3C1 gene polymorphisms
6. NR3C1 genetic defects
6.1. Primary generalized glucocorticoid resistance or Chrousos syndrome
6.2. Primary generalized glucocorticoid hypersensitivity syndrome
7. Recent advances in tissue glucocorticoid sensitivity
8. Conclusions and future perspectives
References
Chapter Fourteen: The androgen receptor
1. Introduction
2. Androgen receptor structure
2.1. Structure of AR domains
2.1.1. DNA-binding domain
2.1.2. Ligand-binding domain
2.2. Structure of AR lacking the N-terminal domain bound to DNA
2.3. Structure of full-length AR
2.4. Remaining questions concerning AR structure
3. Androgen receptor signaling
3.1. Interaction with chaperone proteins
3.2. Post-translational modification
3.3. Dimerization
3.4. Binding to DNA
3.5. Differential transcription by AR agonists
3.6. Allostery in AR signaling
3.7. Termination of androgen signaling
4. Androgen receptor splice variants
4.1. N-terminal truncation
4.2. CAG repeats
4.3. AR splice variants
4.3.1. Mechanisms of AR-SV expression
4.3.2. AR-SV expression in patients
4.3.3. AR-V7 and therapy resistance
4.3.4. Non-genomic effects of AR-SVs
5. Androgen receptor detection & quantitation
5.1. AR-SV specific antibodies
5.2. Application of mass spectrometry (MS)
6. Androgen receptor pharmacology
6.1. Androgenic vs anabolic effects
6.2. Selective androgen receptor modulators (SARMs)
6.3. Androgen receptor antagonists
6.4. Androgen deprivation therapy re-thought
6.5. PROTACs-proteolysis targeting chimera
6.6. N-terminal domain antagonists
6.7. DNA-binding antagonists
6.8. Peptidomimetic targeting of co-activator region LxxLL motifs
6.9. Bromodomain/BET inhibitors, CBP/p300 inhibitors
6.10. Bifunctional agents
6.10.1. Galeterone
6.10.2. BMT4-158
6.10.3. GTX-560
6.10.4. Indomethacin
6.10.5. MF-15
7. Conclusions and future directions
Acknowledgments
References
Chapter Fifteen: Steroid-receptor coactivator complexes in thyroid hormone-regulation of Xenopus metamorphosis
1. Introduction
2. Transcriptional regulation by TR and its dual functions in Xenopus development
3. A role of histone acetylation in gene regulation by TR
4. Critical involvement of steroid-receptor coactivator complexes in regulating metamorphosis by liganded TR
5. Conclusion
Acknowledgment
References
Chapter Sixteen: Essential and subtype-dependent function of thyroid hormone receptors during Xenopus metamorphosis
1. Introduction
2. Molecular mechanisms of gene regulation by TR and their implications in Xenopus development
3. Molecular and transgenic studies on TR in Xenopus laevis
4. Gene knockout studies in Xenopus tropicalis
4.1. A critical role of TRa in controlling premetamorphic tadpole growth and metamorphic timing
4.2. Spatiotemporal effects of individual TR knockout correlate with their expression profiles
4.3. TR is required for larval tissue resorption but not for the development of most, if not all, adult organs
5. Conclusion
Acknowledgment
References
Chapter Seventeen: Steroid hormone signaling: What we can learn from insect models
1. Introduction
2. Phylogenetic relationships of biosynthetic pathways and nuclear receptors
2.1. Steroidogenic enzymes in insects and mammals
2.2. Nuclear receptors for steroid hormones in insects and mammals
3. Cholesterol homeostasis
3.1. Regulation of cholesterol homeostasis by nuclear receptors in mammals
3.2. Regulation of cholesterol homeostasis by nuclear receptors in insects
4. Hormone transport mechanisms
4.1. Transporter-mediated cellular uptake of thyroid hormones
4.2. Elimination of intracellular steroid hormones by efflux transporters
4.3. Facilitated diffusion of ecdysteroids in insects
5. Concluding remarks
Acknowledgments
References
Chapter Eighteen: Membrane estrogen receptor and follicle-stimulating hormone receptor
1. Gonadotropins and estrogens in ovarian physiology
2. Expression and physiology of the FSH receptor
3. The membrane estrogen receptor is expressed in the ovary
4. A new view of antral follicular growth
5. Physiological significance of FSHR and GPER co-expression in the ovary
6. Conclusions
Acknowledgments
References
Chapter Nineteen: Structure-function of DHEA binding proteins
1. Introduction
2. DHEA binds steroid hormone receptors
3. DHEA activates hepatic nuclear receptors
4. DHEA activates G-protein-coupled receptors (GPCRs)
5. DHEA activates GPER1
6. DHEA inhibits T-type Ca channels: CaV3.1, CaV3.2 or CaV3.3
7. DHEA is an agonist for TRPM3
8. DHEA and DHEA-S are neurosteroids
9. DHEA-S action via chaperone protein SIG-1R
10. DHEA binds NGFR and TRKA
11. DHEA and mitochondrial function
12. Conclusions and future directions
References
Chapter Twenty: Juvenile hormone receptor Methoprene tolerant: Functions and applications
1. Introduction
2. JH receptor discovery
3. Two JH receptor genes identified in fruit flies, moths and butterflies
4. JH receptor functions-RNAi studies
5. JH receptor functions-gene editing studies
6. Development of JH receptor-based applications in agriculture and medicine
7. Conclusions and future directions
Acknowledgments
References
Chapter Twenty-One: Structural dynamics of chemokine receptors
1. Chemokine receptors
2. CXCR4 and CCR5
2.1. CXCR4 antagonists
2.2. CCR5 antagonists
2.3. CXCR4 agonists
2.4. CCR5 agonists
3. Conclusions and future directions
Acknowledgments
References

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