A5068870089- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Bacteriophages and microbial interactions
- interferon and immune responses
- SARS-CoV-2 and COVID-19 Research
- Lipid Membrane Structure and Behavior
- Protein Structure and Dynamics
- Viral gastroenteritis research and epidemiology
- Bacterial Genetics and Biotechnology
- Enzyme Structure and Function
- HIV Research and Treatment
- Viral Infections and Outbreaks Research
- Mosquito-borne diseases and control
- Surfactants and Colloidal Systems
- ATP Synthase and ATPases Research
- Alzheimer's disease research and treatments
- Spectroscopy and Quantum Chemical Studies
- Heat shock proteins research
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Virus-based gene therapy research
- vaccines and immunoinformatics approaches
- Porphyrin and Phthalocyanine Chemistry
- Photodynamic Therapy Research Studies
- Respiratory viral infections research
Centro Nacional de Biotecnología
2012-2025
Universidad Autónoma de Madrid
2005-2023
Consejo Superior de Investigaciones Científicas
2010-2023
Biocom
2018
Unidades Centrales Científico-Técnicas
2013
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine
2008-2009
Institute for Research in Biomedicine
2009
Universidade de Santiago de Compostela
2009
Instituto de Ciencia de Materiales de Madrid
2009
Institut de Ciència de Materials de Barcelona
2008
We describe the isolation and detailed structural characterization of stable toxic oligomers α-synuclein that have accumulated during process amyloid formation. Our approach has allowed us to identify distinct subgroups probe their molecular architectures by using cryo-electron microscopy (cryoEM) image reconstruction techniques. Although exist in a range sizes, with different extents nature β-sheet content exposed hydrophobicity, they all possess hollow cylindrical architecture similarities...
The influenza viruses cause annual epidemics of respiratory disease and occasional pandemics, which constitute a major public-health issue. segmented negative-stranded RNAs are associated with the polymerase complex nucleoprotein (NP), forming ribonucleoproteins (RNPs), responsible for virus transcription replication. We describe structure native RNPs derived from virions. They show double-helical conformation in two NP strands opposite polarity each other along helix. Both connected by...
The influenza viruses contain a segmented, single-stranded RNA genome of negative polarity. Each segment is encapsidated by the nucleoprotein and polymerase complex into ribonucleoprotein particles (RNPs), which are responsible for virus transcription replication. Despite their importance, information about structure these RNPs scarce. We have determined three-dimensional biologically active recombinant RNP cryo-electron microscopy. shows nonameric ring (at 12 Angstrom resolution) with two...
Abstract Here we report the characterization of 17T2, a SARS-CoV-2 pan-neutralizing human monoclonal antibody isolated from COVID-19 convalescent individual infected during first pandemic wave. 17T2 is class 1 VH1-58/κ3-20 antibody, derived receptor binding domain (RBD)-specific IgA + memory B cell, with broad neutralizing activity against former and new variants, including XBB.1.16 BA.2.86 Omicron subvariants. Consistently, demonstrates in vivo prophylactic therapeutic BA.1.1 infection...
Most bacterial viruses need a specialized machinery, called "tail," to inject their genomes inside the cytoplasm without disrupting cellular integrity. Bacteriophage T7 is well characterized member of Podoviridae family infecting Escherichia coli, and it has short noncontractile tail that assembles sequentially on viral head after DNA packaging. The complex around 2.7 MDa composed at least four proteins as follows: connector (gene product 8, gp8), tubular gp11 gp12, fibers (gp17). Using...
Alphaviruses are emerging positive-stranded RNA viruses which replicate and transcribe their genomes in membranous organelles formed the cell cytoplasm. The nonstructural protein 1 (nsP1) is responsible for viral capping gates replication by assembling into monotopic membrane-associated dodecameric pores. pathway unique to Alphaviruses; beginning with N7 methylation of a guanosine triphosphate (GTP) molecule, followed covalent linkage an m7GMP group conserved histidine nsP1 transfer this cap...
The formation and full characterization of single self-assembling α,γ-peptide nanotubes (α,γ-SPNs) is described. introduction C60 into cyclic peptides allows the preparation supramolecular 1D fullerene arrangements induced by peptide nanotube under appropriate conditions.
Pulmonary surfactant is a lipid-protein complex essential to stabilize alveoli, by forming surface active films able reach and sustain very low tensions (< 2 mN m(-1)) during the film compression that occurs at end-expiration. The particular lipid composition of surfactant, including high proportion dipalmitoylphosphatidylcholine (DPPC), induces segregation fluid ordered disordered phases in membranes physiological temperatures. DPPC-enriched phase has been related with ability produce...
The emergence of SARS-CoV-2 variants that escape from immune neutralization are challenging vaccines and antibodies developed to stop the COVID-19 pandemic. Thus, it is important establish therapeutics directed toward multiple or specific variants. envelope spike (S) glycoprotein key target neutralizing (Abs). We selected a panel nine nanobodies (Nbs) dromedary camels immunized with receptor-binding domain (RBD) S, engineered Nb fusions as humanized heavy chain Abs (hcAbs). Nbs derived hcAbs...
The S:A222V point mutation, within the G clade, was characteristic of 20E (EU1) SARS-CoV-2 variant identified in Spain early summer 2020. This mutation has since reappeared Delta subvariant AY.4.2, raising questions about its specific effect on viral infection. We report combined serological, functional, structural and computational studies characterizing impact this mutation. Our results reveal that promotes an increased RBD opening slightly increases ACE2 binding as compared to parent...
Abstract Supramolecular assemblies are integral to cellular biochemical processes, relying on their dynamic nature fulfill essential functions. The protease ClpP1P2, paired with ATPase partners ClpC1 or ClpX, is vital for the survival of Mycobacterium tuberculosis ( Mtb ). While ClpP1P2 complex requires activation by specific N-blocked dipeptides (e.g., Z-Leu-Leu) exhibit proteolytic activity in vitro, mechanism vivo remains unclear. In this study, we identified novel activators that enabled...
Abstract All organisms depend on specific proteins to compact and organize their genomes. In eukaryotes, histones fulfil this role, while bacterial chromosomes are shaped by nucleoid-associated (NAPs). Among its pleiotropic functions, the NAP Hfq plays a pivotal role in genome organization. study, we characterized structure of C-terminal extension Hfq, which mediates chromosomal compaction, DNA-bound state. Using an integrative approach that combined transmission electron microscopy, neutron...
The unfoldase ClpC1 is one of the most exciting drug targets against tuberculosis. This AAA+ works in cooperation with ClpP1P2 protease and target at least four natural product antibiotics: cyclomarin, ecumicin, lassomycin, rufomycin. Although these molecules are promising starting points for development, their mechanisms action remain largely unknown. Taking advantage a middle domain mutant, we determined first structure Mycobacterium tuberculosis its apo, cyclomarin-, ecumicin-bound states...
Nanoscopic and uniform unilamellar vesicles, rich in cholesterol, have been prepared by a new procedure, named "DELOS-SUSP", which is based on the depressurization of cholesterol solution CO2-expanded acetone into an aqueous containing surfactant. The CO2 used here as cosolvent medium, allowing straightforward preparation vesicular systems with controlled size distribution, shape, stability unachievable conventional mixing technologies. resulting nanoscopic dispersed water were characterized...
Abstract Photodynamic treatment with different photosensitizers (PSs) can result in the specific induction of apoptosis many cell types. It is commonly accepted that this apoptotic response depends on mitochondrial accumulation PS. Accumulation other cellular organelles, such as lysosomes or Golgi complex, and subsequent photodamage resulting an process has been also described. However, role played by adhesion induced epithelial cells after photodynamic not well characterized. Here, we have...
The broadly neutralizing 2F5 and 4E10 monoclonal antibodies (MAbs) recognize epitopes within the membrane-proximal external region (MPER) that connects human immunodeficiency virus type 1 (HIV-1) envelope gp41 ectodomain with transmembrane anchor. By adopting different conformations stably insert into virion membrane interface, such as helical structures, a conserved aromatic-rich sequence MPER is thought to participate in HIV-1-cell fusion. Recent experimental evidence suggests activity of...
RuvB-Like transcription factors function in cell cycle regulation, development and human disease, such as cancer heart hyperplasia. The mechanisms that regulate adenosine triphosphate (ATP)-dependent activity, oligomerization post-translational modifications this family of enzymes are yet unknown. We present the first crystallographic structure full-length RuvBL2 which provides novel insights into its mechanistic action biology. ring-shaped hexameric presented here resolves for time mobile...
Microcin E492 (MccE492) is a pore-forming bacteriocin produced and exported by Klebsiella pneumoniae RYC492. Besides its antibacterial activity, excreted MccE492 can form amyloid fibrils in vivo as well vitro. It has been proposed that bacterial amyloids be functional playing biological role, the particular case of it would control activity. fibril's morphology formation kinetics vitro have well-characterized, however, not known which amino acid residues determine amyloidogenic propensity,...