Articles tagged with G Protein Coupled Receptors
Scientists have identified three powerful, drug-like molecules that directly target beta-arrestins, the first clear way to control these proteins with pharmacological precision. The compounds block beta-arrestin interaction with GPCRs and carry out their normal functions, allowing signaling through G proteins to persist.
Researchers at Duke University School of Medicine identified a new mechanism by which G protein-coupled receptors (GPCRs) control signaling in cells. They found that β-arrestin proteins can assemble into liquid-like clusters known as condensates, acting as hubs to organize signaling molecules.
A multi-institutional team led by Sanford Burnham Prebys aims to develop a non-opioid pain therapeutic using lead molecule SBI-810. The effort, funded by a $3.9 million NIH grant, seeks to optimize the compound into a drug that could provide effective pain relief without addiction risks.
Researchers investigated the binding thermodynamics of doxepin geometric isomers to the histamine H1 receptor, revealing differences in enthalpy and entropy contributions. The study highlights the importance of considering conformational constraints in designing ligands with optimized thermodynamic properties.
Researchers at St. Jude Children's Research Hospital found that distinct GPCR ligands create different levels of activation by pushing the receptor through its activation steps at varying speeds. This affects the efficacy of agonists, with partial agonists getting stuck in kinetic traps and releasing G-proteins more slowly.
Researchers at Sanford Burnham Prebys discovered a new mechanism to confer signaling bias in predictable ways, permitting rational design of new drugs. This breakthrough could lead to better therapies for addiction and psychiatric disorders by targeting the neurotensin receptor 1 (NTSR1) with biased modulators.
Adhesion G protein-coupled receptors (aGPCRs) use a self-cleavage process to monitor their function. This process relies on multiple domain-extrinsic factors, ensuring efficient receptor activation and preventing faulty proteins from reaching the cell surface. The discovery provides new insights into how cells maintain quality control.
Researchers at the University of Oklahoma have made a significant breakthrough in understanding the amylin hormone, which controls appetite and blood sugar. Their findings provide new tools for drug development, enabling pharmaceutical companies to target specific receptors with greater precision.
Scientists at Leipzig University have discovered that the adhesion G protein-coupled receptor GPR133 plays a central role in building and maintaining healthy bone. By mimicking natural activation, a new active substance AP503 can strengthen bones and potentially treat osteoporosis.
The study reveals the structure and activation mechanism of the human EP1 receptor, a key player in pain, cardiovascular disease, and certain cancers. The researchers identified unique residues that form a distinct binding motif for prostaglandin E2 and uncovered subtype-specific activation mechanisms.
Scientists developed a data science framework to understand how cells travel through the body by analyzing chemokines and G protein-coupled receptors. They found that specific positions in structured and disordered regions determine how these proteins bind, allowing for rational alteration of cell migration.
A new study reveals that specific gut bacteria can break down certain drugs, altering their efficacy. The research found that 30 out of 127 tested drugs were heavily metabolized by human gut microbiota, potentially reducing their effectiveness. The study's findings could have significant implications for personalized medicine and drug ...
Researchers have identified new gateways for drugs to modulate proteins regulating cellular activity. These discoveries may facilitate the creation of new medications or improve existing ones, leading to more targeted therapies and reduced side effects.
A team of scientists developed a computational design tool called SPaDES to create new membrane receptors that outperform natural counterparts. The new receptors were designed by optimizing water-mediated interactions, resulting in higher stability and signaling efficiency.
Researchers discovered novel regulatory molecules in adipogenesis, specifically membrane receptors like GPCRs. ADGRD1 promotes differentiation of adipose progenitor cells while GPR39 inhibits this process.
G protein-coupled receptors can form heteromers, affecting ligand binding properties and downstream signaling pathways. Recent advances in live cell imaging techniques provide crucial information on physical interactions in GPCR heteromers.
Researchers at UChicago captured complete images of adhesion G protein-coupled receptors, revealing their complex extracellular region's interaction with the transmembrane region. The findings suggest alternative means of activating the receptor without separating the GAIN domain.
Researchers at Stanford University have developed a new synthetic receptor, PAGER, that can accommodate a broader range of inputs and produce a more diverse set of outputs. The tool enables control of neuronal activity, immune responses, and therapeutic treatments in lab experiments.
A new study introduces a novel approach to mapping GPCR-RAMP interactions, expanding understanding of these interactions and their therapeutic potential. The technique allows researchers to parse out each RAMP's effect on every GPCR, supercharging drug development.
The study elucidated the mechanisms behind G protein selectivity and efficacy in the human adenosine A2A receptor, discovering changes in activation conformations as the primary cause of coupling promiscuity. The research team used experimental and computational techniques to understand allosteric mechanisms and their role in selective...
Researchers at the Lewis Katz School of Medicine will investigate how injured heart cells communicate with other cells throughout the body using microvesicles known as exosomes. The study aims to understand how specific molecules, such as microRNAs, facilitate communication pathways between cells in the heart and vasculature.
The study highlights the importance of protease-activated receptors (PARs) in cancer growth and development, with PH-binding motifs identified as a key platform for drug design. The researchers suggest that targeting PARs could provide an alternative to current oncogenic pathways.
A research team has made a significant breakthrough in understanding the GPR156 receptor protein's role in maintaining auditory function. The study reveals that GPR156 exhibits sustained activity even without external stimuli, highlighting its potential as a target for treating congenital hearing impairments.
The study reveals how opioid receptors stabilize a state for effective signal transmission, making superagonists potent and dangerous. It also highlights the importance of understanding molecular interactions for drug development and developing safer medicines.
Scientists at St. Jude Children's Research Hospital have discovered that only about 80 amino acids in the β2-adrenergic receptor contribute to its pharmacological properties, with specific residues controlling efficacy and potency. Understanding these molecular origins can help design more potent and efficacious drugs.
Researchers train AI to analyze data from over 100 cellular drug targets and their genetic variations. The algorithm predicts with more than 80% accuracy how cell surface receptors respond to drug-like molecules.
Scientists have developed a technique to restore the function of human-derived GPCR proteins in yeast cells, which could accelerate research and lead to more effective treatments. The approach, using error-prone polymerase chain reaction, introduces random mutations that enhance protein stability and function.
The study determined the cryo-electron microscopy structures of class B glucagon receptor bound to β-arrestin 1, revealing a unique tail conformation that differs from previously known arrestin-bound GPCR structures. This new mechanism may enable the development of novel biased ligands with pathway selectivity.
A team from the University of Ottawa has developed a comprehensive screening platform and cellular interrogation tool to facilitate novel drug discovery targeting various human diseases. The 'Tango-Trio' platform can identify small molecule modulators for orphan GPCRs, which have significant untapped therapeutic potential.
Scientists discovered a novel method to activate G protein-coupled receptors from inside cells, which can help develop drugs with fewer or no side effects. This new process uses a non-peptide message molecule called PCO371 that binds to the intracellular region of the receptor and interacts directly with G protein subunits.
Researchers found that GPR141 enhances cell migration and proliferation in breast cancer by activating the p-mTOR/p53 signaling pathway. Silencing GPR141 restores p53 expression and attenuates tumor growth, suggesting its role in regulating breast cancer progression and metastasis.
Researchers at UNIGE discovered that natural opioids cannot enter cells, whereas therapeutic opioids can, leading to differences in physiological responses. The study's findings could help develop safer medications with improved efficacy and reduced side effects.
Researchers have identified a potential breakthrough in improving drug delivery by targeting the third intracellular loop of G protein-coupled receptors. This unique mechanism could enable more precise control over cellular signaling outcomes, leading to far more targeted therapeutics.
Researchers from Universität Leipzig have developed a molecular sensor system to detect when and where adhesion GPCRs break apart, activating receptors and transmitting biochemical signals. The breakthrough could lead to the development of drugs targeting these receptors for treating various diseases.
Researchers at Okayama University discovered genes and proteins responsible for the rapid contraction of axopodia in Heliozoa, a group of eukaryotes. The study identified key players in microtubule disruption, including katanin p60, kinesin, and calcium signaling proteins.
Researchers from City of Hope identified how a protein receptor targeted by 33% of all federally approved medications works. This discovery could facilitate pharmaceutical research and lead to the creation of innovative medicines with fewer side effects.
A new study identifies nitric oxide as a key molecule in the β2-adrenergic receptor feedback loop, mediating airway relaxation. The research team discovered that preventing nitric oxide's feedback mechanism leads to a powerful airway relaxant. Mice with a specific mutation in the β2 AR gene are resistant to bronchoconstriction and asthma.
Researchers have identified a molecular mechanism behind worm olfaction, revealing how they discriminate between over 1,300 scents despite having only 32 olfactory neurons. The discovery involves the conserved protein arrestin, which helps fine-tune multiple sensations in both worms and humans.
Researchers have gained new insight into how GPCRs operate, a step toward developing improved drugs. By probing the beta-adrenergic receptor, they uncovered details about β-arrestin activation by GPCRs, which could lead to pathway-specific compounds.
Researchers used single-molecule imaging to study GPCR activation, gaining insight into cellular signal relay and potential drug targets for various disorders. The findings show that the receptor tail plays an autoinhibitory role, controlled by agonist binding, which affects signaling intensity and duration.
Research in Nature reveals the intrinsic activation mechanism of orphan GPCRs, a family offering new opportunities for cancer drug development. The study uncovers key molecular factors governing receptor activation and function modulation.
Researchers have captured the first real-time signaling cascade of a wild-type receptor in its native membrane environment using mass spectrometry. The study reveals the impact of lipids on rhodopsin signaling and regeneration, demonstrating potential new targets for therapeutic value in the visual system.
Scientists have found complex signaling pathways in cells, using a technique called fluorescence microscopy to visualize nanodomains beneath the cell membrane. These domains can be thought of as pop-up factories that process signals from receptors on the cell surface.
Researchers at the University of Houston have identified a new biomarker, NPY1R, that predicts therapy outcome and has potential as a drug target in estrogen receptor-positive breast cancer. The study found that NPY1R expression is associated with favorable outcomes in Luminal A subtype breast cancer, but declines in resistant cases.
A Tel Aviv University study found a significant link between changes in G-protein-coupled receptors and brain adaptability. Disabling the voltage sensor of these proteins caused uncontrolled brain flexibility, leading to excessive habituation to odors.
Researchers at PSI have developed a platform to measure biased signalling in G protein-coupled receptors (GPCRs), enabling selective therapeutic effects and fewer side effects. By testing specially designed bivalent ligands, they can bias signalling towards desired pathways.
A UCI-led team has developed a high-throughput screen methodology to identify compounds that affect the functional role of Rh, a key G protein-coupled receptor. The study reveals new allosteric modulators that can alter rod light response kinetics or reduce rod sensitivity, paving the way for next-generation therapeutics.
A recent study reveals that protein HSP27 plays a crucial role in regulating blood vessel leakage, which is a hallmark of sepsis. By targeting HSP27, researchers hope to develop drugs that can stabilize blood vessel barriers and prevent fluid loss.
Scientists have discovered how neurotransmitters and proteins interact to trigger neuronal responses in the brain, with implications for understanding mood disorders and addictions. The study reveals small changes in protein connections control cellular responses, enabling precise regulation of neurotransmitter effects.
Researchers at Ruhr-University Bochum have developed a new reverse optogenetic tool that can be controlled by light, suitable for studying changes in the brain responsible for epilepsy.
Scientists have discovered a way to control brain circuits using a protein called parapinopsin, found in lamprey. This breakthrough could lead to new treatments for mood disorders and unwanted behaviors.
Researchers have developed a new imaging technique that captures individual receptors on the surface of living cells with unprecedented detail. This breakthrough could lead to a new generation of drugs with greater specificity and reduced side effects, particularly for disorders such as schizophrenia and depression.
Scientists at Temple University and Case Western Reserve University will explore the role of nitric oxide in controlling the beta-adrenergic receptor system, a key player in heart function. The insights gained could lead to new therapies for congestive heart failure.
A multinational team discovered at least two inactive and three active conformations of the human adenosine A2A receptor, dependent on ligands and G protein interactions. The study sheds new light on GPCR activation and signaling, offering opportunities for drug discovery.
Studies have revealed that the journey of a nascent protein to become a mature cell surface receptor involves multiple steps and complex interactions with proteins such as C1orf27, HCR1, and GGA3. Understanding these mechanisms is crucial for optimizing hormone and drug use targeting GPCRs.
A comprehensive study of RGS proteins reveals how they modulate cell signaling and explains why people's responses to the same drugs can vary widely. The researchers created a roadmap for how GPCR signals are routed in cells, highlighting the potential for new treatment approaches for various conditions.
Researchers at Duke University developed a synthetic molecule that selectively dampens cocaine-induced hyperactivity and interferes with dopamine metabolism in the brain's rewards center. The treatment slowed down drug use by 20 minutes to an hour and reduced consumption by over 80 percent in mice.
Researchers at MIPT have developed a method to combine structural and spectroscopic approaches for studying membrane receptors. This allows for a detailed understanding of receptor functioning and behavior inside the cell, which is crucial for developing effective drugs.
Researchers at Stanford University School of Engineering used computer simulations to discover how to minimize side effects in a broad class of drugs targeting G protein-coupled receptors. By designing new molecules, they can alter the receptor's shape to deliver beneficial effects while avoiding side effects.
A USC-led team of scientists has discovered the precise shape of the melanocortin 4 receptor, a key player in human metabolism. The findings could lead to more effective therapies for obesity and other metabolic diseases, which affect millions worldwide.