Search results for: Arnau Cordomi

Items from 1 to 20 out of 27 results

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Discovery of a macromolecular complex mediating the hunger suppressive actions of cocaine: Structural and functional properties

Mireia Casanovas, Mireia Jiménez‐Rosés, Arnau Cordomí, Alejandro Lillo, more

Cocaine not only increases brain dopamine levels but also activates the sigma₁ receptor (σ₁R) that in turn regulates orexigenic receptor function. Identification of interactions involving dopamine D₁ (D₁R), ghrelin (GHS‐R_1a), and σ₁ receptors have been addressed by biophysical techniques and a complementation approach using interfering peptides. The effect of cocaine on receptor functionality was...

article

Discovery of Homobivalent Bitopic Ligands of the Cannabinoid CB₂ Receptor**

Paula Morales, Gemma Navarro, Marc Gómez‐Autet, Laura Redondo, more

Chemistry – A European Journal > 26 > 68 > 15839 - 15842

Single chemical entities with potential to simultaneously interact with two binding sites are emerging strategies in medicinal chemistry. We have designed, synthesized and functionally characterized the first bitopic ligands for the CB₂ receptor. These compounds selectively target CB₂ versus CB₁ receptors. Their binding mode was studied by molecular dynamic simulations and site‐directed mutagenesis.

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Cocaine Blocks Effects of Hunger Hormone, Ghrelin, Via Interaction with Neuronal Sigma-1 Receptors

David Aguinaga, Mireia Medrano, Arnau Cordomí, Mireia Jiménez-Rosés, more

Molecular Neurobiology > 2019 > 56 > 2 > 1196-1210

Despite ancient knowledge on cocaine appetite-suppressant action, the molecular basis of such fact remains unknown. Addiction/eating disorders (e.g., binge eating, anorexia, bulimia) share a central control involving reward circuits. However, we here show that the sigma-1 receptor (σ₁R) mediates cocaine anorectic effects by interacting in neurons with growth/hormone/secretagogue (ghrelin) receptors...

article

Cross-communication between G_i and G_s in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain

Gemma Navarro, Arnau Cordomí, Marc Brugarolas, Estefanía Moreno, more

BMC Biology > 2018 > 16 > 1 > 1-15

Background G-protein-coupled receptor (GPCR) heteromeric complexes have distinct properties from homomeric GPCRs, giving rise to new receptor functionalities. Adenosine receptors (A₁R or A_2AR) can form A₁R-A_2AR heteromers (A₁-A_2AHet), and their activation leads to canonical G-protein-dependent (adenylate cyclase mediated) and -independent (β-arrestin mediated) signaling. Adenosine has different affinities...

article

Molecular Switches of Allosteric Modulation of the Metabotropic Glutamate 2 Receptor

Laura Pérez-Benito, Maarten L.J. Doornbos, Arnau Cordomí, Luc Peeters, more

Structure > 2017 > 25 > 7 > 1153-1162.e4

Metabotropic glutamate (mGlu) receptors are class C G protein-coupled receptors (GPCRs) crucial for CNS function and important drug discovery targets. Glutamate triggers receptor activation from an extracellular domain binding site while allosteric modulators bind in the seven-transmembrane domain. Little is known about how allosteric modulators produce their functional effects at the molecular level...

article

Gut hormone GPCRs: structure, function, drug discovery

Arnau Cordomí, Daniel Fourmy, Irina G Tikhonova

Current Opinion in Pharmacology > 2016 > 31 > C > 63-67

Crystallization and determination of the high resolution three-dimensional structure of the β2-adrenergic receptor in 2007 was followed by structure elucidation of a number of other receptors, including those for neurotensin and glucagon. These major advances foster the understanding of structure–activity relationship of these receptors and structure-based rational design of new ligands having more...

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Analysis of the interactions of sulfur‐containing amino acids in membrane proteins

José C. Gómez‐Tamayo, Arnau Cordomí, Mireia Olivella, Eduardo Mayol, more

Protein Science > 25 > 8 > 1517 - 1524

The interactions of Met and Cys with other amino acid side chains have received little attention, in contrast to aromatic–aromatic, aromatic–aliphatic or/and aliphatic–aliphatic interactions. Precisely, these are the only amino acids that contain a sulfur atom, which is highly polarizable and, thus, likely to participate in strong Van der Waals interactions. Analysis of the interactions present in...

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Beyond spectral tuning: human cone visual pigments adopt different transient conformations for chromophore regeneration

Sundaramoorthy Srinivasan, Arnau Cordomí, Eva Ramon, Pere Garriga

Cellular and Molecular Life Sciences > 2016 > 73 > 6 > 1253-1263

Human red and green visual pigments are seven transmembrane receptors of cone photoreceptor cells of the retina that mediate color vision. These pigments share a very high degree of homology and have been assumed to feature analogous structural and functional properties. We report on a different regeneration mechanism among red and green cone opsins with retinal analogs using UV–Vis/fluorescence spectroscopic...

article

Quaternary structure of a G-protein-coupled receptor heterotetramer in complex with G_i and G_s

Gemma Navarro, Arnau Cordomí, Monika Zelman-Femiak, Marc Brugarolas, more

BMC Biology > 2016 > 14 > 1 > 1-12

Background G-protein-coupled receptors (GPCRs), in the form of monomers or homodimers that bind heterotrimeric G proteins, are fundamental in the transfer of extracellular stimuli to intracellular signaling pathways. Different GPCRs may also interact to form heteromers that are novel signaling units. Despite the exponential growth in the number of solved GPCR crystal structures, the structural properties...

article

Structures for G-Protein-Coupled Receptor Tetramers in Complex with G Proteins

Arnau Cordomí, Gemma Navarro, María S. Aymerich, Rafael Franco

Trends in Biochemical Sciences > 2015 > 40 > 10 > 548-551

G-Protein-coupled receptors (GPCRs) were classically described as monomers. We now appreciate that they also function as homo- and hetero-oligomers, for which structural information is lacking. Here, we use available 3D structures and biochemical considerations to present and evaluate experimentally testable structural models for GPCR oligomers and associated G proteins.

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TMalphaDB and TMbetaDB: web servers to study the structural role of sequence motifs in α-helix and β-barrel domains of membrane proteins

Marc Perea, Ivar Lugtenburg, Eduardo Mayol, Arnau Cordomí, more

BMC Bioinformatics > 2015 > 16 > 1 > 1-6

Background Membrane proteins represent over 25 % of human protein genes and account for more than 60 % of drug targets due to their accessibility from the extracellular environment. The increasing number of available crystal structures of these proteins in the Protein Data Bank permits an initial estimation of their structural properties. Description We have developed two web servers—TMalphaDB for...

article

Functional elements of the gastric inhibitory polypeptide receptor: Comparison between secretin- and rhodopsin-like G protein-coupled receptors

Arnau Cordomí, Sadek Ismail, Minos-Timotheos Matsoukas, Chantal Escrieut, more

Biochemical Pharmacology > 2015 > 96 > 3 > 237-246

Innovative crystallographic techniques have resulted in an exponential growth in the number of solved G-protein coupled receptor (GPCR) structures and a better understanding of the mechanisms of class A receptor activation and G protein binding. The recent release of the type 1 receptor for the corticotropin-releasing factor and the glucagon receptor structures, two members of the secretin-like family,...

article

Ligand-G Protein Allosteric Communication through Internal Waters in GPCR Complexes

Roman Osman, Jose Carlos Gomez, Mihaly Mezei, Dov Barak, more

Biophysical Journal > 2015 > 108 > 2 Supplement 1 > 363a-364a

article

Binding Specificity of Retinal Analogs to Photoactivated Visual Pigments Suggest Mechanism for Fine-Tuning GPCR-Ligand Interactions

Sundaramoorthy Srinivasan, Eva Ramon, Arnau Cordomí, Pere Garriga

Chemistry & Biology > 2014 > 21 > 3 > 369-378

11-cis-retinal acts as an inverse agonist stabilizing the inactive conformation of visual pigments, and upon photoactivation, it isomerizes to all-trans-retinal, initiating signal transduction. We have analyzed opsin regeneration with retinal analogs for rhodopsin and red cone opsin. We find differential binding of the analogs to the receptors after photobleaching and a dependence of the binding kinetics...

article

Sulfur-containing amino acids in 7TMRs: molecular gears for pharmacology and function

Arnau Cordomí, José C. Gómez-Tamayo, Véronique Gigoux, Daniel Fourmy

Trends in Pharmacological Sciences > 2013 > 34 > 6 > 320-331

Seven-transmembrane receptors (7TMRs) mediate the majority of physiological responses to hormones and neurotransmitters in higher organisms. Tertiary structure stability and activation of these versatile membrane proteins require formation or disruption of complex networks of well-recognized interactions (such as H-bonds, ionic, or aromatic–aromatic) but also of other type of interactions which have...

article

The Role of Internal Water in GPCR Complexes

Roman Osman, Mihaly Mezei, Dov Barak, Arnau Cordomi, more

Biophysical Journal > 2013 > 104 > 2 Supplement 1 > 41a

article

Distinct conformational states of the CCK2R are associated with β-arrestin-2 recruitment or phospholipase-C activation

Rémi Magnan, Chantal Escrieut, Véronique Gigoux, Kavita De, more

Regulatory Peptides > 2012 > 177 > Supplement > S27-S28

article

Chemical Probes for the Recognition of Cannabinoid Receptors in Native Systems

Lidia Martín‐Couce, Mar Martín‐Fontecha, Óscar Palomares, Leyre Mestre, more

Angewandte Chemie > 124 > 28 > 7002 - 7005

Rezeptoren sichtbar gemacht: Die beschriebenen biotinmarkierten niedermolekularen Sonden mit exzellenten Affinitäten für den CB₁‐ und CB₂‐Cannabinoid‐Rezeptor (CB₁R und CB₂R) ermöglichen die direkte Visualisierung dieser Rezeptoren in nativen zellulären Systemen einschließlich Neuronen (siehe Bild), Mikroglia und Immunzellen. Die Methode könnte helfen, die Komplexität des endogenen Cannabinoidsystems...

article

Chemical Probes for the Recognition of Cannabinoid Receptors in Native Systems

Lidia Martín‐Couce, Mar Martín‐Fontecha, Óscar Palomares, Leyre Mestre, more

Angewandte Chemie International Edition > 51 > 28 > 6896 - 6899

Receptors made visible: The described biotin‐tagged small‐molecule probes with excellent affinities for the CB₁ and CB₂ cannabinoid receptors (CB₁R and CB₂R) enable direct visualization of these receptors in native cellular systems, including neurons (see picture), microglia, and immune cells. This method could overcome some of the limitations of current methodologies and may help to dissect the complexity...

article

Alterations in the photoactivation pathway of rhodopsin mutants associated with retinitis pigmentosa

Laia Bosch‐Presegué, Eva Ramon, Darwin Toledo, Arnau Cordomí, more

The FEBS Journal > 278 > 9 > 1493 - 1505

The visual photoreceptor rhodopsin undergoes a series of conformational changes upon light activation, eventually leading to the active metarhodopsin II conformation, which is able to bind and activate the G‐protein, transducin. We have previously shown that mutant rhodopsins G51V and G89D, associated with retinitis pigmentosa, present photobleaching patterns characterized by the formation of altered...

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Search results for: Arnau Cordomi

Discovery of a macromolecular complex mediating the hunger suppressive actions of cocaine: Structural and functional properties

Discovery of Homobivalent Bitopic Ligands of the Cannabinoid CB₂ Receptor**

Cocaine Blocks Effects of Hunger Hormone, Ghrelin, Via Interaction with Neuronal Sigma-1 Receptors

Cross-communication between G_i and G_s in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain

Molecular Switches of Allosteric Modulation of the Metabotropic Glutamate 2 Receptor

Gut hormone GPCRs: structure, function, drug discovery

Analysis of the interactions of sulfur‐containing amino acids in membrane proteins

Beyond spectral tuning: human cone visual pigments adopt different transient conformations for chromophore regeneration

Quaternary structure of a G-protein-coupled receptor heterotetramer in complex with G_i and G_s

Structures for G-Protein-Coupled Receptor Tetramers in Complex with G Proteins

TMalphaDB and TMbetaDB: web servers to study the structural role of sequence motifs in α-helix and β-barrel domains of membrane proteins

Functional elements of the gastric inhibitory polypeptide receptor: Comparison between secretin- and rhodopsin-like G protein-coupled receptors

Ligand-G Protein Allosteric Communication through Internal Waters in GPCR Complexes

Binding Specificity of Retinal Analogs to Photoactivated Visual Pigments Suggest Mechanism for Fine-Tuning GPCR-Ligand Interactions

Sulfur-containing amino acids in 7TMRs: molecular gears for pharmacology and function

The Role of Internal Water in GPCR Complexes

Distinct conformational states of the CCK2R are associated with β-arrestin-2 recruitment or phospholipase-C activation

Chemical Probes for the Recognition of Cannabinoid Receptors in Native Systems

Chemical Probes for the Recognition of Cannabinoid Receptors in Native Systems

Alterations in the photoactivation pathway of rhodopsin mutants associated with retinitis pigmentosa

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