A5005585216- Cardiomyopathy and Myosin Studies
- Force Microscopy Techniques and Applications
- Cellular Mechanics and Interactions
- Marine Invertebrate Physiology and Ecology
- RNA and protein synthesis mechanisms
- Marine Sponges and Natural Products
- Biochemical and Structural Characterization
- RNA Research and Splicing
- Lipid Membrane Structure and Behavior
- Mechanical and Optical Resonators
- Molecular Junctions and Nanostructures
- Cellular transport and secretion
- Muscle Physiology and Disorders
- Erythrocyte Function and Pathophysiology
- Marine Toxins and Detection Methods
- Protein Structure and Dynamics
- Advanced Electron Microscopy Techniques and Applications
- Microtubule and mitosis dynamics
- Toxin Mechanisms and Immunotoxins
- Transgenic Plants and Applications
- Cardiovascular Effects of Exercise
- RNA modifications and cancer
- Biotin and Related Studies
- Cardiac Fibrosis and Remodeling
- Bacterial Genetics and Biotechnology
Spanish National Centre for Cardiovascular Research
2016-2025
Instituto de Salud Carlos III
2023
Columbia University
2009-2016
Universidad Complutense de Madrid
2004-2013
The NAD + precursor nicotinamide improves diastolic dysfunction caused by aging, hypertension, or metabolic syndrome in rodents.
The active site of the Haloalkane Dehydrogenase (HaloTag) enzyme can be covalently attached to a chloroalkane ligand providing mechanically strong tether, resistant large pulling forces. Here we demonstrate covalent tethering protein L and I27 polyproteins between an atomic force microscopy (AFM) cantilever glass surface using HaloTag anchoring at one end thiol chemistry other end. Covalent is unambiguously confirmed by observation full length polyprotein unfolding, combined with high...
In the early stages of an infection, pathogenic bacteria use long fibrous structures known as pili adhesive anchors for attachment to host cells. These also play key roles in colony and biofilm formation. all those processes, must withstand large mechanical forces. The nasty gram-positive human pathogen Streptococcus pyogenes are assembled single, micrometer tandem modular proteins covalently linked repeats pilin proteins. Here we single molecule force spectroscopy techniques study...
The response of titin to mechanical forces is a major determinant the function heart. When placed under pulling force, unstructured regions uncoil while its immunoglobulin (Ig) domains unfold and extend. Using single-molecule atomic force microscopy, we show that disulfide isomerization reactions within Ig enable third mechanism elasticity. Oxidation leads non-canonical bonds stiffen enabling force-triggered more extended states domains. sequence structural analyses, 21% titin's I-band...
Significance Bacteria colonizing the oropharynx must adhere despite mechanical challenges from coughing, sneezing, and chewing; however, little is known about how Gram-positive organisms achieve this feat. We studied pilus adhesive proteins two report a conserved mechanism for dissipating energy of perturbation. The are stable up to forces 525 pN 690 pN, respectively, making these most mechanically known. After perturbation, refold rapidly at low force, resulting in large hysteresis with...
Cells remodel their structure in response to mechanical strain. However, how forces are translated into biochemical signals that coordinate the structural changes observed at plasma membrane (PM) and underlying cytoskeleton during mechanoadaptation is unclear. Here, we show PM controlled by a tension-sensing pathway composed of c-Abl tyrosine kinase curvature regulator FBP17. FBP17 recruited caveolae induce formation caveolar rosettes. deficient cells have reduced rosette density, lack...
Abstract Single-molecule methods using recombinant proteins have generated transformative hypotheses on how mechanical forces are and sensed in biological tissues. However, testing these their natural environment remains inaccesible to conventional tools. To address this limitation, here we demonstrate a mouse model carrying HaloTag-TEV insertion the protein titin, main determinant of myocyte stiffness. Using our system, specifically sever titin by digestion with TEV protease, find that...
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. Variants in MYBPC3, gene encoding myosin-binding protein C (cMyBP-C), are leading cause of HCM. However, pathogenicity status hundreds MYBPC3 variants found patients remains unknown, as a consequence our incomplete understanding pathomechanisms triggered by HCM-causing variants. Here, we examined 44 nontruncating that classified HCM-linked or nonpathogenic according to cosegregation and population genetics...
COVID-19-specific vaccines are efficient prophylactic weapons against SARS-CoV-2 virus. However, boosting innate responses may represent an innovative way to immediately fight future emerging viral infections or boost vaccines. MV130 is a mucosal immunotherapy, based on mixture of whole heat-inactivated bacteria, that has shown clinical efficacy recurrent respiratory infections. Herein, we show the intranasal administration this immunotherapy confers heterologous protection infection in...
BACKGROUND: How the sarcomeric complex is continuously turned over in long-living cardiomyocytes unclear. According to prevailing model of sarcomere maintenance, sarcomeres are maintained by cytoplasmic soluble protein pools with free recycling between and sarcomeres. METHODS: We imaged quantified turnover expressed endogenous proteins, including giant titin, culture vivo, at single cell level using pulse-chase labeling Halo-tagged proteins covalent ligands. RESULTS: disprove pool instead...