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Author: Antoine Koehl Publisher: ISBN: Category : Languages : en Pages :
Book Description
G protein coupled receptors (GPCRs) are a class of cell-surface receptors that mediate complex cellular responses to a myriad of physiological stimuli, from photons and neurotransmitters, to hormones, peptides, and even full proteins. GPCR signaling underlies almost all of physiology; this central importance to human health and disease is reflected in the fact that approximately 30% of all FDA approved drugs target GPCRs. Ligand action at GPCRs mediates intracellular signaling through heterotrimeric G proteins, as well as G protein-independent pathways. Over the past decade, a structural framework has allowed for a more precise understanding of ligand-mediated activation in rhodopsin-like GPCRs, as well as the molecular mechanism for GPCR signaling through the stimulatory G protein, Gs. My work expands this structural understanding of GPCR activation and signaling by exploring two novel signaling systems in the GPCR family for which structural information is lacking. First, I describe work on the structure of a peptide-activated mu-opioid receptor (muOR) in complex with the inhibitory G protein, Gi. As signaling through Gi is responsible for the beneficial aspects of opioids, the structure of this complex can help guide the design and discovery of novel therapeutics with reduced liabilities. I then show the structural mechanism of activation in a family C GPCR, the metabotropic glutamate receptor 5 (mGlu5). Family C receptors are unusual in that, as well as the GPCR-defining 7-transmembrane (7TM) domain, they possess relatively large amino-terminal extracellular domains (ECDs) that form obligate dimers and contain the orthosteric ligand-binding sites. Taken together, this work presents novel insights into GPCR activation and signaling.
Author: Antoine Koehl Publisher: ISBN: Category : Languages : en Pages :
Book Description
G protein coupled receptors (GPCRs) are a class of cell-surface receptors that mediate complex cellular responses to a myriad of physiological stimuli, from photons and neurotransmitters, to hormones, peptides, and even full proteins. GPCR signaling underlies almost all of physiology; this central importance to human health and disease is reflected in the fact that approximately 30% of all FDA approved drugs target GPCRs. Ligand action at GPCRs mediates intracellular signaling through heterotrimeric G proteins, as well as G protein-independent pathways. Over the past decade, a structural framework has allowed for a more precise understanding of ligand-mediated activation in rhodopsin-like GPCRs, as well as the molecular mechanism for GPCR signaling through the stimulatory G protein, Gs. My work expands this structural understanding of GPCR activation and signaling by exploring two novel signaling systems in the GPCR family for which structural information is lacking. First, I describe work on the structure of a peptide-activated mu-opioid receptor (muOR) in complex with the inhibitory G protein, Gi. As signaling through Gi is responsible for the beneficial aspects of opioids, the structure of this complex can help guide the design and discovery of novel therapeutics with reduced liabilities. I then show the structural mechanism of activation in a family C GPCR, the metabotropic glutamate receptor 5 (mGlu5). Family C receptors are unusual in that, as well as the GPCR-defining 7-transmembrane (7TM) domain, they possess relatively large amino-terminal extracellular domains (ECDs) that form obligate dimers and contain the orthosteric ligand-binding sites. Taken together, this work presents novel insights into GPCR activation and signaling.
Author: Mario Tiberi Publisher: Humana Press ISBN: 9781493991204 Category : Science Languages : en Pages : 406
Book Description
This detailed volume assembles comprehensive protocols to assist with the study of structural, molecular, cell biological, and in vivo facets of GPCRs, and to enable the development of experimental tools for screening novel GPCR drugs. Sections explore the tweaking of ligands, bioluminescence and FRET approaches, specific GPCR signaling properties, as well as visualization of subcellular compartmentalization. Written for the highly successful Methods in Molecular Biology series, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, G Protein-Coupled Receptor Signaling: Methods and Protocols serves as an ideal reference for life scientists working in a variety of research fields including molecular pharmacology, cell and developmental biology, brain behavior and physiology, drug development and screening. Chapter 4 is available open access under a CC BY 4.0 license via link.springer.com.
Author: Jeffrey L. Benovic Publisher: Wiley-Liss ISBN: 9780471252771 Category : Medical Languages : en Pages : 0
Book Description
Recent advances in molecular and cell biology enabling the cloning, expression, and mutagenesis of signal transduction proteins has prompted an explosion of knowledge in the field of receptor regulation, facilitating the discovery of new classes of regulatory proteins, and providing a basis and means for manipulating receptor function through multiple intracellular targets. This volume covers methods used to examine how the function(s) of receptors are regulated. Understanding how to regulate the function and expression of these receptors is critical in determining how to modify receptors and to translocating receptors away from the cell surface and its recycling. Individual chapters focus on specific techniques used to characterize receptors (epitope tagging, measurement and analysis of receptor phosphorylation, analysis of the kinetics of receptor desensitization, and assessment of receptor/G protein coupling); the role of regulatory proteins (receptor kinases and phosphatases, arrestins) in modulating receptor function; and the methods used to measure receptor trafficking (ligand binding, immunofluoresence) and expression (transcriptional and translational regulation). * Covers a broad range of important concepts and methodologies which are current in the study of G protein-coupled receptors (GPCRs) * G-protein coupled receptors make up over 40% of the current pharmacological targets * Provides detailed protocols for executing various strategies and offers informed judgments as to what approaches are and aren't useful * Volume Editor, Jeffrey Benovic, is a dominant world leader in the study of receptor regulation of GPCR kinases and is highly respected in the field
Author: Jesus Giraldo Publisher: Royal Society of Chemistry ISBN: 1849733449 Category : Science Languages : en Pages : 549
Book Description
G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors, with more than 800 members identified thus far in the human genome. They regulate the function of most cells in the body, and represent approximately 3% of the genes in the human genome. These receptors respond to a wide variety of structurally diverse ligands, ranging from small molecules, such as biogenic amines, nucleotides and ions, to lipids, peptides, proteins, and even light. Ligands (agonists and antagonists) acting on GPCRs are important in the treatment of numerous diseases, including cardiovascular and mental disorders, retinal degeneration, cancer, and AIDS. It is estimated that these receptors represent about one third of the actual identified targets of clinically used drugs. The determination of rhodopsin crystal structure and, more recently, of opsin, 1 and 2 adrenergic and A2A adenosine receptors provides both academia and industry with extremely valuable data for a better understanding of the molecular determinants of receptor function and a more reliable rationale for drug design. GPCR structure and function constitutes a hot topic. The book, which lies between the fields of chemical biology, molecular pharmacology and medicinal chemistry, is divided into three parts. The first part considers what receptor structures tell us about the mechanism of receptor activation. Part II focuses on receptor function. It discusses what the data from biophysical and mutational studies, and the analysis of the interactions of the receptor with ligands and regulator proteins, tell us about the process of signal transduction. The final part, on modelling and simulation, details new insights on the link between structure and mechanism and their implications in drug design.
Author: Stephen Sprang Publisher: Academic Press ISBN: 0080552692 Category : Science Languages : en Pages : 262
Book Description
This volume in the Advances in Protein Chemistry series features cutting-edge articles on topics in protein chemistry. This volume includes chapters on the structural basis of effector regulation and signal termination in heterotrimeric Gƒуnƒnproteins; How do receptors activate G proteins; Some mechanistic insights into GPCR activation from detergent solubilized ternary complexes on beads; Activation of G protein coupled receptors; Kinetic analysis of g-protein-coupled receptor signaling using fluorescence resonance energy transfer in living cells; Regulation of Rho Guanine Nucleotide Exchange Factors (RhoGEFs) by G proteins.
Author: Guillaume Lebon Publisher: Springer ISBN: 3030245918 Category : Science Languages : en Pages : 289
Book Description
This book introduces readers to the latest advances in G protein-coupled receptor (GPCR) biology. It reviews our current understanding of the structural basis of ligand binding and allosteric mechanisms, following a decade of technological breakthroughs. Several examples of structure-based drug discovery are presented, together with the future challenges involved in designing better drugs that target GPCRs. In turn, the book illustrates the important concept of GPCR biased signaling in physiological contexts, and presents fluorescent- and light-based methodologies frequently used to measure GPCR signaling or to trace their dynamics in cells upon ligand activation. Taken together, the chapters provide an essential overview and toolkit for new scientific investigators who plan to develop GPCR projects. All chapters were written by experts in their respective fields, and share valuable insights and powerful methodologies for the GPCR field.
Author: Lakshmi A. Devi Publisher: Springer Science & Business Media ISBN: 1592599192 Category : Medical Languages : en Pages : 414
Book Description
A comprehensive survey of the many recent advances in the field of G protein-coupled receptors (GPCR). The authors describe the current knowledge of GPCR receptor structure and function, the different mechanisms involved in the regulation of GPCR function, and the role of pharmacological chaperones in GPCR folding and maturation. They also present new findings about how GPCR dimerization/oligomerization modifies the properties of individual receptors and show how recent developments are leading to significant advances in drug discovery, such as the detection of ligands for orphan GPCRs. Also discussed are the most recent developments that could lead to new drug discoveries: the role of GPCRs in mediating pain, the development of receptor-type selective drugs based on the structural plasticity of receptor activation, and the identification of natural ligands of orphan GPCRs (deorphanization) as possible drug targets.
Author: Publisher: Elsevier ISBN: 0323994350 Category : Science Languages : en Pages : 194
Book Description
G Protein-Coupled Receptors, Part B, Volume 195 represents the largest class of cell H103 surface proteins that have intricate involvement in nearly every physiological process in our body. Approximately one third of the clinically prescribed medicines target GPCRs and the quest to improve the exiting GPCR-targeting therapeutics continues. Sections in this volume include Adhesion G protein-coupled receptors: Structure and functions, Molecular and cellular mechanisms underlying brain region-specific cannabinoid receptor modulation by estradiol across the rodent estrus cycle, Probing the orphan receptors: Tools and directions, Asymmetric activation of Class C GPCRs, Common and selective signal transduction mechanisms of GPCRs, and much more. Covers a broad range of topics related to GPCR activation and signaling Provides several receptor systems, with an emphasis on emerging paradigms Includes different processes and model systems, with a focus on GPCRs
Author: Antonino Belfiore Publisher: Springer ISBN: 9783319446745 Category : Medical Languages : en Pages : 0
Book Description
This volume provides comprehensive coverage of the current knowledge of the physiology of the endocrine system and hormone synthesis and release, transport, and action at the molecular and cellular levels. It presents essential as well as in-depth information of value to both medical students and specialists in Endocrinology, Gynecology, Pediatrics, and Internal Medicine. Although it is well established that the endocrine system regulates essential functions involved in growth, reproduction, and homeostasis, it is increasingly being recognized that this complex regulatory system comprises not only hormones secreted by the classic endocrine glands but also hormones and regulatory factors produced by many organs, and involves extensive crosstalk with the neural and immune system. At the same time, our knowledge of the molecular basis of hormone action has greatly improved. Understanding this complexity of endocrine physiology is crucial to prevent endocrine disorders, to improve the sensitivity of our diagnostic tools, and to provide the rationale for pharmacological, immunological, or genetic interventions. It is such understanding that this book is designed to foster.
Author: D. C. Rees Publisher: Academic Press ISBN: 9780120342211 Category : Languages : en Pages :
Book Description
This volume in the Advances in Protein Chemistry series features cutting-edge articles on topics in protein chemistry. This volume includes chapters on the structural basis of effector regulation and signal termination in heterotrimeric G?n?nproteins; How do receptors activate G proteins; Some mechanistic insights into GPCR activation from detergent solubilized ternary complexes on beads; Activation of G protein coupled receptors; Kinetic analysis of g-protein-coupled receptor signaling using fluorescence resonance energy transfer in living cells; Regulation of Rho Guanine Nucleotide Exchange Factors (RhoGEFs) by G proteins.
Author: Antoine Koehl
Author: Antoine Koehl
Author: Mario Tiberi
Author: Jeffrey L. Benovic
Author: Jesus Giraldo
Author: Stephen Sprang
Author: Guillaume Lebon
Author: Lakshmi A. Devi
Author: 
Author: Antonino Belfiore
Author: D. C. Rees