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Lipid gpcr

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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
#1
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
#2
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
#3
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
#4
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...
September 15, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28884954/native-desorption-electrospray-ionization-liberates-soluble-and-membrane-protein-complexes-from-surfaces
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28508109/solvent-accessibility-of-discrete-residue-positions-in-the-polypeptide-hormone-glucagon-by-19-f-nmr-observation-of-4-fluorophenylalanine
#16
Yaguang Hou, Wanhui Hu, Xiaona Li, John J Skinner, Dongsheng Liu, Kurt Wüthrich
The amino acid 4-fluoro-L-phenylalanine (4F-Phe) was introduced at the positions of Phe6 and Phe22 in the 29-residue polypeptide hormone glucagon by expressing glucagon in E. coli in the presence of an excess of 4F-Phe. Glucagon regulates blood glucose homeostasis by interaction with the glucagon receptor (GCGR), a class B GPCR. By referencing to the 4F-Phe chemical shifts at varying D2O concentrations, the solvent exposure of the two Phe sites along the glucagon sequence was determined, showing that 4F-Phe6 was fully solvent exposed and 4F-Phe22 was only partially exposed...
May 2017: Journal of Biomolecular NMR
https://www.readbyqxmd.com/read/28473666/the-palmitoylation-of-the-n-terminal-extracellular-cys37-mediates-the-nuclear-translocation-of-vpac1-contributing-to-its-anti-apoptotic-activity
#17
Rongjie Yu, Hongyu Liu, Xinhe Peng, Yue Cui, Suqin Song, Like Wang, Huahua Zhang, An Hong, Tianhong Zhou
VPAC1 is class B G protein-coupled receptors (GPCR) shared by pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP). The first cysteine (Cys37) in the N-terminal extracellular domain of mature VPAC1 is a free Cys not involved in the formation of conserved intramolecular disulfide bonds. In order to investigate the biological role of this Cys37 in VPAC1, the wild-type VPAC1 and Cys37/Ala mutant (VPAC1-C37/A) were expressed stably as fusion proteins with enhanced yellow fluorescent protein (EYFP) respectively in Chinese hamster ovary (CHO) cells...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28442430/design-and-purification-of-active-truncated-phosphoinositide-3-kinase-gamma-protein-constructs-for-structural-studies
#18
A Vujičić Žagar, L Scapozza, O Vadas
Phosphoinositide 3-kinase gamma (PI3Kγ) is a lipid kinase that plays a crucial role in cell migration, chemotaxis, oxidative burst and myocardial contractility. It is activated downstream of G protein-coupled receptors (GPCRs) and small GTPases of Ras superfamily. PI3Kγ is a heterodimer composed of a catalytic and a regulatory subunit that is expressed mostly in hematopoietic cells and in the heart. Although it has attracted a lot of attention because of its link with tumor inflammation and heart diseases, its regulation is still not fully understood...
July 2017: Protein Expression and Purification
https://www.readbyqxmd.com/read/28432958/membrane-fusion-between-baculovirus-budded-virus-enveloped-particles-and-giant-liposomes-generated-using-a-droplet-transfer-method-for-the-incorporation-of-recombinant-membrane-proteins
#19
Misako Nishigami, Takaaki Mori, Masahiro Tomita, Kingo Takiguchi, Kanta Tsumoto
Giant proteoliposomes are generally useful as artificial cell membranes in biochemical and biophysical studies, and various procedures for their preparation have been reported. We present here a novel preparation technique that involves the combination of i) cell-sized lipid vesicles (giant unilamellar vesicles, GUVs) that are generated using the droplet-transfer method, where lipid monolayer-coated water-in-oil microemulsion droplets interact with oil/water interfaces to form enclosed bilayer vesicles, and ii) budded viruses (BVs) of baculovirus (Autographa californica nucleopolyhedrovirus) that express recombinant transmembrane proteins on their envelopes...
April 13, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28374590/binding-site-characterization-of-am1336-a-novel-covalent-inverse-agonist-at-human-cannabinoid-2-receptor-using-mass-spectrometric-analysis
#20
Srikrishnan Mallipeddi, Simion Kreimer, Nikolai Zvonok, Kiran Vemuri, Barry L Karger, Alexander R Ivanov, Alexandros Makriyannis
Cannabinoid 2 receptor (CB2R), a Class-A G-protein coupled receptor (GPCR), is a promising drug target under a wide array of pathological conditions. Rational drug design has been hindered due to our poor understanding of the structural features involved in ligand binding. Binding of a high-affinity biarylpyrazole inverse agonist AM1336 to a library of the human CB2 receptor (hCB2R) cysteine-substituted mutants provided indirect evidence that two cysteines in transmembrane helix-7 (H7) were critical for the covalent attachment...
June 19, 2017: Journal of Proteome Research
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