Download Free G Protein Coupled Receptor Dimers Book in PDF and EPUB Free Download. You can read online G Protein Coupled Receptor Dimers and write the review.

G-protein-coupled receptors (GPCRs) are believed to be the largest family of membrane proteins involved in signal transduction and cellular responses. They dimerize (form a pair of macromolecules) with a wide variety of other receptors. The proposed book will provide a comprehensive overview of GPCR dimers, starting with a historical perspective and including, basic information about the different dimers, how they synthesize, their signaling properties, and the many diverse physiological processes in which they are involved. In addition to presenting information about healthy GPCR dimer activity, the book will also include a section on their pathology and therapeutic potentials.
G-protein-coupled receptors (GPCRs) are believed to be the largest family of membrane proteins involved in signal transduction and cellular responses. They dimerize (form a pair of macromolecules) with a wide variety of other receptors. The proposed book will provide a comprehensive overview of GPCR dimers, starting with a historical perspective and including, basic information about the different dimers, how they synthesize, their signaling properties, and the many diverse physiological processes in which they are involved. In addition to presenting information about healthy GPCR dimer activity, the book will also include a section on their pathology and therapeutic potentials.
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.
"G protein-coupled receptors (GPCRs) represent a large class of membrane receptors that mediate cellular communication events in cells. GPCRs are widely targeted by therapeutics, but their downstream signaling events remain incompletely understood, especially in the context of homo- and heterodimers. The dimerization of GPCRs can affect not only the nature and strength of downstream signaling pathways but also the trafficking of receptors to the membrane as well as their internalization kinetics. This project focuses on three GPCRs that are implicated in the regulation of blood pressure: the angiotensin II type 1 receptor (AT1R), the prostaglandin F receptor (FP), and the [beta]2-adrenoreceptor ([beta]2AR), and how their downstream canonical pathways intertwine in the context of identified heterodimeric receptors. To investigate their interactomes, we will use the engineered ascorbate peroxidase 2 (APEX2) genetically fused to the C-tail of these GPCRs. APEX2 is a promiscuous biotin ligase that allows the labeling and subsequent identification of proximal proteins. Our main objective is to identify novel interactors of the AT1R-FP and AT1R-[beta]2AR dimers. This will support our hypothesis that GPCR heterodimers have different interactomes than GPCR monomers or homodimers. Our first aim was to validate the expression and function of the APEX2-tagged constructs in HEK 293F cells. We confirmed APEX2 activity through western blotting with streptavidin-HRP and immunofluorescence with neutravidin. We also used immunofluorescence to verify that the receptors reached the plasma membrane, utilizing an HA tag that each receptor-APEX2 construct has on its N-terminus. To confirm that the APEX2-tagged receptors still couple functionally to the G protein heterotrimer, we used Bioluminescence Resonance Energy Transfer (BRET)-based biosensors. The activation of [beta]2AR leads to an increase in cAMP levels through G[alpha]s, which subsequently binds to an EPAC-based biosensor and causes a change in BRET. The activation of either AT1R-APEX2 or FP-APEX2 leads to an increase in intracellular Ca++ through G[alpha]q, which binds to the Calflux biosensor and causes a change in BRET. Next, we will investigate the interactomes of heterodimers under control and stimulated conditions at different time points by co-expressing APEX2-tagged receptors with putative heterodimer partners. We will enrich the biotinylated proteins using streptavidin-coated sepharose beads, followed by on bead trypsin digestion. Proteins will be identified by label-free mass spectrometry and confirmed by co-immunoprecipitation"--
This volume has a strong focus on homo-oligomerization, which is surprisingly common. However, protein function is so often linked to both homo- and hetero-oligomerization and many heterologous interactions likely evolved from homologous interaction, so this volume also covers many aspects of hetero-oligomerization.
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.
G protein coupled receptors (GPCRs) are a superfamily of transmembrane proteins responsible for transducing extracellular stimuli into intracellular responses. GPCRs are indispensable to a vast variety of distinct physiologies and behaviors and represent approximately 50% of all human drug targets. However, considerable debate exists as to the structural basis for GPCR activation, with a classical monomeric (two state model) conflicting with a growing number of reports indicating that these receptors form higher order functional oligomers. These receptor-receptor interactions can impact receptor trafficking, ligand sensitivity, desensitization, and strength of effector response. As such, an understanding of GPCR oligomerization is indispensable to our overall understanding of receptor dynamics. Additionally, the specific molecular events underlying receptor activation and signaling remain incompletely understood. Since the initial discovery of the GPCR receptor family, a number of conserved amino acid motifs have been identified that have been shown to play specific and critical roles in GPCR activation, intracellular G-protein coupling, and receptor desensitization. Still, many of these motifs remain incompletely described, with some motifs having only been evaluated in a small subset of receptors, and experimental evidence suggests that in some cases, these conserved motifs may have divergent roles in specific receptor subfamilies. As such, the conservation of these motifs throughout GPCR evolution represents and interesting and unresolved aspect of GPCR function. The goal of this research was two-fold. In one study, I utilized a combination of bioinformatics, site-directed mutagenesis, signaling assays, and fluorescent microscopy techniques to evaluate the functional role and evolutionary conservation of a specific amino acid motif, the WxFG motif, which is present in approximately 90% of all Class A receptors. Our investigation showed that, in contrast to previous studies of this motif, disruption of the WxFG motif results in trafficking defects across a range of GPCRs representing multiple Class A GPCR subfamilies, regardless of taxa. A second study evaluated whether Drosophila GPCRs, specifically a subset of neuropeptide receptors, assembled as higher order structures at the plasma membrane. While there have been many receptors shown to assemble as dimers or oligomers at the plasma membrane since the phenomenon was first recognized over two decades ago, the majority of these studies focused on vertebrate GPCRs, and the question of whether invertebrate GPCRs show similar phenotypes has been poorly evaluated, and to date, no Drosophila GPCR has been empirically demonstrated to assemble as a dimer. To gain a deeper understanding of GPCR molecular assembly, I evaluated multiple Drosophila receptors utilizing FRET microscopy to determine both the prevalence of GPCR dimerization among Drosophila neuropeptide receptors, and determine whether dimerization is conserved across taxa in specific receptor subfamilies. This investigation showed that all Drosophila GPCRs tested were able to assemble as homodimers when expressed in a heterologous expression system, suggesting that not only do Drosophila GPCRs likely assemble as higher order structures at the plasma membrane, but also that the phenomenon of receptor dimerization is an ancient property of the receptor superfamily that has been conserved throughout GPCR evolution. Taken together, these investigations further our understanding of the molecular events underlying GPCR signaling, and suggest that many aspects of receptor function are not taxa specific, and are likely fundamental features of GPCR function that have been conserved throughout the evolution of this receptor superfamily.
Catalogues major facts about receptors, G-proteins and effector molecules. Each entry has a common format, using a minimum amount of text, and contains information on the sequence, gene structure, distribution, agonists/antagonists and physiochemical properties of these proteins.