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Lipid gpcr

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https://www.readbyqxmd.com/read/29212811/altered-expression-of-hepatic-%C3%AE-adrenergic-receptors-in-aging-rats-implications-for-age-related-metabolic-dysfunction-in-liver
#1
Yun Shi, Zhen-Ju Shu, Hanzhou Wang, Jeffrey L Barnes, Chih-Ko Yeh, Paramita M Ghosh, Michael S Katz, Amrita Kamat
Increased β-adrenergic receptor (β-AR)-mediated activation of adenylyl cyclase (AC) in rat liver during aging has been linked to age-related increases in hepatic glucose output and hepatosteatosis. In this study we investigated the expression of β-ARs, individual receptor subtypes, and G protein-coupled receptor (GPCR) regulatory proteins in livers from aging rats. Radioligand binding studies demonstrated that β-AR density increased by >3-fold in hepatocyte membranes from senescent (24 mo old) compared to young adult (7 mo old) rats, and that this phenomenon was blocked by food restriction which is known to retard aging processes in rodents...
December 6, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29211777/alpha-conotoxin-buia-globular-isomer-is-a-competitive-antagonist-for-oleoyl-l-alpha-lysophosphatidic-acid-binding-to-lpar6-a-molecular-dynamics-study
#2
Saima Younis, Sajid Rashid
Lysophosphatidic acid receptor 6 (LPAR6) is a G-protein coupled receptor (GPCR) involved in hair development and cytoskeleton formation in mammals. Its proliferation is implicated in several forms of cancer including liver cancer, squamous cell carcinoma and metastatic prostate cancer. Current study emphasizes the isolation of competitive non-lipid and stable peptide antagonists for Lysophosphatidic acid ligand. A total of 148 conotoxin structures were characterized for their binding abilities against LPAR6...
2017: PloS One
https://www.readbyqxmd.com/read/29209002/the-orientation-and-stability-of-the-gpcr-arrestin-complex-in-a-lipid-bilayer
#3
Dali Wang, Hua Yu, Xiangdong Liu, Jianqiang Liu, Chen Song
G protein-coupled receptors (GPCRs) constitute a large family of membrane proteins that plays a key role in transmembrane signal transduction and draw wide attention since it was discovered. Arrestin is a small family of proteins which can bind to GPCRs, block G protein interactions and redirect signaling to G-protein-independent pathways. The detailed mechanism of how arrestin interacts with GPCR remains elusive. Here, we conducted molecular dynamics simulations with coarse-grained (CG) and all-atom (AA) models to study the complex structure formed by arrestin and rhodopsin, a prototypical GPCR, in a POPC bilayer...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29198881/role-of-arsenic-exposure-in-adipose-tissue-dysfunction-and-its-possible-implication-in-diabetes-pathophysiology
#4
REVIEW
Kaviyarasi Renu, Harishkumar Madhyastha, Radha Madhyastha, Masugi Maruyama, Sankarganesh Arunachlam, Abilash V G
Exposure to arsenic in drinking water can stimulate a diverse number of diseases that originate from impaired lipid metabolism in adipose and glucose metabolism, leading to insulin resistance. Arsenic inhibits differentiation of adipocyte and mediates insulin resistance with diminutive information on arsenicosis on lipid storage and lipolysis. This review focused on different mechanisms and pathways involved in adipogenesis and lipolysis in adipose tissue during arsenic-induced diabetes. Though arsenic is known to cause type2 diabetes through different mechanisms, the role of adipose tissue in causing type2 diabetes is still unclear...
November 30, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29154090/proliferative-and-metastatic-roles-for-phospholipase-d-in-mouse-models-of-cancer
#5
REVIEW
Eric Roth, Michael A Frohman
Phospholipase D (PLD) activity has been proposed to facilitate multiple steps in cancer progression including growth, metabolism, angiogenesis, and mobility. The canonical enzymes PLD1 and PLD2 enact their diverse effects through hydrolyzing the membrane lipid phosphatidylcholine to generate the second messenger and signaling lipid phosphatidic acid (PA). However, the widespread expression of PLD1 and PLD2 in normal tissues and the additional distinct enzymatic mechanisms through which PA can be generated have produced uncertainty regarding the optimal settings in which PLD inhibition might ameliorate cancer...
November 14, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/28993767/genomic-programming-of-human-neonatal-dendritic-cells-in-congenital-systemic-and-in-vitro-cytomegalovirus-infection-reveal-plastic-and-robust-immune-pathway-biology-responses
#6
Widad Dantoft, Pablo Martínez-Vicente, James Jafali, Lara Pérez-Martínez, Kim Martin, Konstantinos Kotzamanis, Marie Craigon, Manfred Auer, Neil T Young, Paul Walsh, Arnaud Marchant, Ana Angulo, Thorsten Forster, Peter Ghazal
Neonates and especially premature infants are highly susceptible to infection but still can have a remarkable resilience that is poorly understood. The view that neonates have an incomplete or deficient immune system is changing. Human neonatal studies are challenging, and elucidating host protective responses and underlying cognate pathway biology, in the context of viral infection in early life, remains to be fully explored. In both resource rich and poor settings, human cytomegalovirus (HCMV) is the most common cause of congenital infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28990386/an-adaptable-phospholipid-membrane-mimetic-system-for-solution-nmr-studies-of-membrane-proteins
#7
Chih-Ta Henry Chien, Lukas R Helfinger, Mark J Bostock, Andras Solt, Yi Lei Tan, Daniel Nietlispach
Based on the saposin-A (SapA) scaffold protein we demonstrate the suitability of a size-adaptable phospholipid membrane-mimetic system for solution NMR studies of membrane proteins under close-to-native conditions. The Salipro nanoparticle size can be tuned over a wide pH range by adjusting the saposin-to-lipid stoichiometry enabling maintenance of sufficiently high amounts of phospholipid in the Salipro nanoparticle to mimic a realistic membrane environment while controlling the overall size to enable solution NMR for a range of membrane proteins...
October 9, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28987925/solubilization-of-the-serotonin1a-receptor-monitored-utilizing-membrane-dipole-potential
#8
Parijat Sarkar, Amitabha Chattopadhyay
Solubilization of membrane proteins by amphiphilic detergents represents a crucial step in studies of membrane proteins in which proteins and lipids in natural membranes are dissociated giving rise to mixed clusters of proteins, lipids and detergents in the aqueous dispersion. Although solubilization is a popular method, physicochemical principles underlying solubilization are not well understood. In this work, we monitored solubilization of the bovine hippocampal serotonin1A receptor, a representative member of the GPCR family, using membrane dipole potential measured by a dual fluorescence ratiometric approach with a potential-sensitive fluorophore...
October 4, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28919559/adipokinetic-hormone-receptor-gene-identification-and-its-role-in-triacylglycerol-mobilization-and-sexual-behavior-in-the-oriental-fruit-fly-bactrocera-dorsalis
#9
Qiu-Li Hou, Er-Hu Chen, Hong-Bo Jiang, Dan-Dan Wei, Shun-Hua Gui, Jin-Jun Wang, Guy Smagghe
Energy homeostasis requires continuous compensation for fluctuations in energy expenditure and availability of food resources. In insects, energy mobilization is under control of the adipokinetic hormone (AKH) where it is regulating the nutritional status by supporting the mobilization of lipids. In this study, we characterized the gene coding for the AKH receptor (AKHR) and investigated its function in the oriental fruit fly (Bactrocera dorsalis) that is economically one of the most important pest insects of tropical and subtropical fruit...
November 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28884954/native-desorption-electrospray-ionization-liberates-soluble-and-membrane-protein-complexes-from-surfaces
#10
Stephen Ambrose, Nicholas G Housden, Kallol Gupta, Jieyuan Fan, Paul White, Hsin-Yung Yen, Julien Marcoux, Colin Kleanthous, Jonathan T S Hopper, Carol V Robinson
Mass spectrometry (MS) applications for intact protein complexes typically require electrospray (ES) ionization and have not been achieved via direct desorption from surfaces. Desorption ES ionization (DESI) MS has however transformed the study of tissue surfaces through release and characterisation of small molecules. Motivated by the desire to screen for ligand binding to intact protein complexes we report the development of a native DESI platform. By establishing conditions that preserve non-covalent interactions we exploit the surface to capture a rapid turnover enzyme-substrate complex and to optimise detergents for membrane protein study...
September 8, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28880957/mapping-the-stk4-hippo-signaling-network-in-prostate-cancer-cell
#11
Damien Ready, Kader Yagiz, Pooneh Amin, Yuksel Yildiz, Vincent Funari, Serdar Bozdag, Bekir Cinar
Dysregulation of MST1/STK4, a key kinase component of the Hippo-YAP pathway, is linked to the etiology of many cancers with poor prognosis. However, how STK4 restricts the emergence of aggressive cancer remains elusive. Here, we investigated the effects of STK4, primarily localized in the cytoplasm, lipid raft, and nucleus, on cell growth and gene expression in aggressive prostate cancer. We demonstrated that lipid raft and nuclear STK4 had superior suppressive effects on cell growth in vitro and in vivo compared with cytoplasmic STK4...
2017: PloS One
https://www.readbyqxmd.com/read/28877377/membrane-cholesterol-effect-on-the-5-ht2a-receptor-insights-into-the-lipid-induced-modulation-of-an-antipsychotic-drug-target
#12
Juan Manuel Ramírez-Anguita, Ismael Rodríguez-Espigares, Ramon Guixà-González, Agostino Bruno, Mariona Torrens-Fontanals, Alejandro Varela-Rial, Jana Selent
The serotonin 5-hydroxytryptamine 2A (5-HT2A ) receptor is a G-protein-coupled receptor (GPCR) relevant for the treatment of CNS disorders. In this regard, neuronal membrane composition in the brain plays a crucial role in the modulation of the receptor functioning. Since cholesterol is an essential component of neuronal membranes, we have studied its effect on the 5-HT2A receptor dynamics through all-atom MD simulations. We find that the presence of cholesterol in the membrane increases receptor conformational variability in most receptor segments...
September 6, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28854168/commensal-bacteria-make-gpcr-ligands-that-mimic-human-signalling-molecules
#13
COMPARATIVE STUDY
Louis J Cohen, Daria Esterhazy, Seong-Hwan Kim, Christophe Lemetre, Rhiannon R Aguilar, Emma A Gordon, Amanda J Pickard, Justin R Cross, Ana B Emiliano, Sun M Han, John Chu, Xavier Vila-Farres, Jeremy Kaplitt, Aneta Rogoz, Paula Y Calle, Craig Hunter, J Kipchirchir Bitok, Sean F Brady
Commensal bacteria are believed to have important roles in human health. The mechanisms by which they affect mammalian physiology remain poorly understood, but bacterial metabolites are likely to be key components of host interactions. Here we use bioinformatics and synthetic biology to mine the human microbiota for N-acyl amides that interact with G-protein-coupled receptors (GPCRs). We found that N-acyl amide synthase genes are enriched in gastrointestinal bacteria and the lipids that they encode interact with GPCRs that regulate gastrointestinal tract physiology...
September 7, 2017: Nature
https://www.readbyqxmd.com/read/28747438/palmitoylation-is-a-prerequisite-for-dimerization-dependent-raftophilicity-of-rhodopsin
#14
Keiji Seno, Fumio Hayashi
The visual photopigment rhodopsin (Rh) is a prototypical G protein-coupled receptor (GPCR) responsible for initiation of the phototransduction cascade in rod photoreceptors. Similar to other GPCRs, Rh can form dimers or even higher oligomers and tends to have a supramolecular organization that is likely important in the dim light response. Rh also exhibits high affinity for lipid rafts (i.e. raftophilicity) upon light-dependent binding with the cognate G protein transducin (Gt), suggesting the presence of lipid raft-like domains in the retinal disk membrane and their importance in phototransduction...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28745020/distinct-roles-of-the-7-transmembrane-receptor-protein-rta3-in-regulating-the-asymmetric-distribution-of-phosphatidylcholine-across-the-plasma-membrane-and-biofilm-formation-in-candida-albicans
#15
Archita Srivastava, Shabnam Sircaik, Farha Husain, Edwina Thomas, Shivani Ror, Sumit Rastogi, Darakshan Alim, Priyanka Bapat, David R Andes, Clarissa J Nobile, Sneh L Panwar
Fungal pathogens such as Candida albicans exhibit several survival mechanisms to evade attack by antifungals and colonise host tissues. Rta3, a member of the Rta1-like family of lipid-translocating exporters has a 7-transmembrane domain topology, similar to the G-protein-coupled receptors and is unique to the fungal kingdom. Our findings point towards a role for the plasma membrane localised Rta3 in providing tolerance to miltefosine, an analogue of alkylphosphocholine, by maintaining mitochondrial energetics...
July 25, 2017: Cellular Microbiology
https://www.readbyqxmd.com/read/28700926/the-energetics-of-chromophore-binding-in-the-visual-photoreceptor-rhodopsin
#16
He Tian, Thomas P Sakmar, Thomas Huber
The visual photoreceptor rhodopsin is a prototypical G-protein-coupled receptor (GPCR) that stabilizes its inverse agonist ligand, 11-cis-retinal (11CR), by a covalent, protonated Schiff base linkage. In the visual dark adaptation, the fundamental molecular event after photobleaching of rhodopsin is the recombination reaction between its apoprotein opsin and 11CR. Here we present a detailed analysis of the kinetics and thermodynamics of this reaction, also known as the "regeneration reaction". We compared the regeneration of purified rhodopsin reconstituted into phospholipid/detergent bicelles with rhodopsin reconstituted into detergent micelles...
July 11, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28687666/domain-specific-control-of-germ-cell-polarity-and-migration-by-multifunction-tre1-gpcr
#17
Michelle G LeBlanc, Ruth Lehmann
The migration of primordial germ cells (PGCs) from their place of origin to the embryonic gonad is an essential reproductive feature in many animal species. In Drosophila melanogaster, a single G protein-coupled receptor, Trapped in endoderm 1 (Tre1), mediates germ cell polarization at the onset of active migration and directs subsequent migration of PGCs through the midgut primordium. How these different aspects of cell behavior are coordinated through a single receptor is not known. We demonstrate that two highly conserved domains, the E/N/DRY and NPxxY motifs, have overlapping and unique functions in Tre1...
September 4, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28609478/purification-of-family-b-g-protein-coupled-receptors-using-nanodiscs-application-to-human-glucagon-like-peptide-1-receptor
#18
Yingying Cai, Yuting Liu, Kelly J Culhane, Brian T DeVree, Yang Yang, Roger K Sunahara, Elsa C Y Yan
Family B G protein-coupled receptors (GPCRs) play vital roles in hormone-regulated homeostasis. They are drug targets for metabolic diseases, including type 2 diabetes and osteoporosis. Despite their importance, the signaling mechanisms for family B GPCRs at the molecular level remain largely unexplored due to the challenges in purification of functional receptors in sufficient amount for biophysical characterization. Here, we purified the family B GPCR human glucagon-like peptide-1 (GLP-1) receptor (GLP1R), whose agonists, e...
2017: PloS One
https://www.readbyqxmd.com/read/28571491/insights-into-unbound-bound-states-of-gpr142-receptor-in-a-membrane-aqueous-system-using-molecular-dynamics-simulations
#19
Aman Chandra Kaushik, Shakti Sahi
G protein coupled receptors (GPCRs) are source machinery in signal transduction pathways and being one of the major therapeutic targets play a significant in drug discovery. GPR142, an orphan GPCR, has been implicated in the regulation of insulin, thereby having a crucial role in Type II diabetes management. Deciphering of the structures of orphan GPCRs (O-GPCRs) offer better prospects for advancements in research in ion translocation and transduction of extracellular signals. As the crystallographic structure of GPR142 is not available in PDB, therefore, threading and abinitio based approaches were used for 3D modeling of GPR142...
June 1, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28547763/new-approaches-towards-the-understanding-of-integral-membrane-proteins-a-structural-perspective-on-g-protein-coupled-receptors
#20
REVIEW
Reinhard Grisshammer
Three-dimensional structure determination of integral membrane proteins has advanced in unprecedented detail our understanding of mechanistic events of how ion channels, transporters, receptors, and enzymes function. This exciting progress required a tremendous amount of methods development, as exemplified here with G protein-coupled receptors (GPCRs): Optimizing the production of GPCRs in recombinant hosts; increasing the probability of crystal formation using high-affinity ligands, nanobodies, and minimal G proteins for co-crystallization, thus stabilizing receptors into one conformation; using the T4 lysozyme technology and other fusion partners to promote crystal contacts; advancing crystallization methods including the development of novel detergents, and miniaturization and automation of the lipidic cubic phase crystallization method; the concept of conformational thermostabilization of GPCRs; and developing microfocus X-ray synchrotron technologies to analyze small GPCR crystals...
August 2017: Protein Science: a Publication of the Protein Society
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