A5040924207- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Protein Kinase Regulation and GTPase Signaling
- Mass Spectrometry Techniques and Applications
- RNA Research and Splicing
- Protein Structure and Dynamics
- Neuroscience and Neuropharmacology Research
- RNA modifications and cancer
- Monoclonal and Polyclonal Antibodies Research
- Melanoma and MAPK Pathways
- Steroid Chemistry and Biochemistry
- Neurotransmitter Receptor Influence on Behavior
- Advanced Proteomics Techniques and Applications
- Pancreatic function and diabetes
- Biomedical Text Mining and Ontologies
- Phosphodiesterase function and regulation
- Insect Resistance and Genetics
- Pharmacological Receptor Mechanisms and Effects
- Machine Learning in Bioinformatics
- Lymphoma Diagnosis and Treatment
- Regulation of Appetite and Obesity
- Sphingolipid Metabolism and Signaling
- Carbohydrate Chemistry and Synthesis
University of Cambridge
2022-2025
MRC Laboratory of Molecular Biology
2018-2023
Philipps University of Marburg
2017-2021
Universitat Pompeu Fabra
2013-2019
Hospital del Mar Research Institute
2014-2019
Municipal Institute for Medical Research
2014-2016
McGill University
2012
Christie (Canada)
2012
G protein-coupled receptors (GPCRs) constitute a functionally diverse protein family and are targets for broad spectrum of pharmaceuticals. Technological progress in X-ray crystallography cryogenic electron microscopy has enabled extensive, high-resolution structural characterisation GPCRs different conformational states. However, as highly dynamic events underlie GPCR signalling, complete understanding functionality requires insights into their dynamics. Here, we present large dataset...
Abstract Cholesterol is a key component of cell membranes with proven modulatory role on the function and ligand-binding properties G-protein-coupled receptors (GPCRs). Crystal structures prototypical GPCRs such as adenosine A 2A receptor (A R) have confirmed that cholesterol finds stable binding sites at surface suggesting an allosteric this lipid. Here we combine experimental computational approaches to show can spontaneously enter R-binding pocket from membrane milieu using same portal...
Abstract Class F receptors are considered valuable therapeutic targets due to their role in human disease, but structural changes accompanying receptor activation remain unexplored. Employing population and cancer genomics data, analyses, molecular dynamics simulations, resonance energy transfer-based approaches mutagenesis, we identify a conserved basic amino acid TM6 that acts as switch mediate activation. Across all tested (FZD 4,5,6,7, SMO), mutation of the confers an increased potency...
The Melanocortin-4 Receptor (MC4R) plays a pivotal role in energy homeostasis. We used human MC4R mutations associated with an increased or decreased risk of obesity to dissect mechanisms that regulate function. Most obesity-associated impair trafficking the plasma membrane (PM), whereas obesity-protecting either accelerate recycling PM decrease internalization, resulting enhanced signaling. do not affect canonical Gαs protein-mediated signaling, previously considered be non-pathogenic,...
Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) bind to extracellular ligands and drugs modulate intracellular responses through conformational changes. Despite their importance as drug targets, the molecular origins of pharmacological properties such efficacy (maximum signaling response) potency (the ligand concentration at half-maximal remain poorly understood for any ligand-receptor-signaling system. We used prototypical adrenaline-β2 adrenergic...
// Clara Esteban-Jurado 1 , David Giménez-Zaragoza 2 Jenifer Muñoz Sebastià Franch-Expósito Miriam Álvarez-Barona 3 Teresa Ocaña Cuatrecasas 4 Sabela Carballal María López-Cerón Maria Marti-Solano 5 Marcos Díaz-Gay Tom van Wezel 6 Antoni Castells Luis Bujanda 7 Judith Balmaña 8 Victoria Gonzalo 9 Gemma Llort 10 Ruiz-Ponte Joaquín Cubiella 11 Francesc Balaguer Rosa Aligué Sergi Castellví-Bel Gastroenterology Department, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer...
Functional selectivity is a property of G protein-coupled receptors that allows them to preferentially couple particular signaling partners upon binding biased agonists. Publication the X-ray crystal structure serotonergic 5-HT1B and 5-HT2B in complex with ergotamine, drug capable activating protein coupling β-arrestin at receptor but clearly favoring over subtype, has recently provided structural insight into this phenomenon. In particular, these structures highlight importance specific...
Detection of biased agonists for the serotonin 5-HT<sub>2A</sub> receptor can guide discovery safer and more efficient antipsychotic drugs. However, rational design such drugs has been hampered by difficulty detecting impact small structural changes on signaling bias. To overcome these difficulties, we characterized dynamics ligand-receptor interactions known balanced using molecular simulations. Our analysis revealed that with residues S5.46 N6.55 discriminate compounds different functional...
Sphingosine-1-phosphate (S1P) is an immunomodulatory lipid mediator that plays important role in lymphocyte trafficking. Elevated levels of S1P are found bronchoalveolar lavage (BAL) fluid patients with asthma; however, its disease not known. FTY720, a synthetic analog S1P, has been shown to abrogate allergic inflammation and airway hyperresponsiveness following acute allergen challenge. However, effects on asthmatic remodeling induced by repeated exposure unknown. Ovalbumin (OVA)-sensitized...
Abstract Codon usage adaptation of lytic viruses to their hosts is determinant for viral fitness. In this work, we analyzed the codon adenoviral proteins by principal component analysis and assessed host. We observed a general clustering according function. However, there was significant variation in preference between host-interacting fiber protein rest structural late phase proteins, with non-optimal fiber. To understand impact bias fiber, optimized Adenovirus-5 hexon protein. The...
Abstract Adaptation is defined as an evolutionary process allowing organisms to succeed in certain habitats or conditions. Chromosomal inversions have the potential be key adaptation processes, since they can contribute maintenance of favoured combinations adaptive alleles through reduced recombination between individuals carrying different inversions. We analysed six genes ( Pif1A, Abi, Sqd, Yrt, Atpα and Fmr1 ), located inside outside three O chromosome European populations Drosophila...