A5037679183- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- Enzyme Structure and Function
- DNA and Nucleic Acid Chemistry
- Inorganic Fluorides and Related Compounds
- Ubiquitin and proteasome pathways
- Synthesis and Reactions of Organic Compounds
- Pharmacological Effects and Toxicity Studies
- Advanced biosensing and bioanalysis techniques
- Neuroscience and Neuropharmacology Research
- Genomics and Chromatin Dynamics
- Nuclear Structure and Function
- Photosynthetic Processes and Mechanisms
- Synthesis and Characterization of Heterocyclic Compounds
- Protein Structure and Dynamics
- Occupational health in dentistry
- Fluorine in Organic Chemistry
- Alzheimer's disease research and treatments
- Ferrocene Chemistry and Applications
- Silicone and Siloxane Chemistry
- Neuroblastoma Research and Treatments
- Computational Drug Discovery Methods
- Protein purification and stability
- Airway Management and Intubation Techniques
Institute of Cancer Research
2021-2025
University Hospital Complex Of Vigo
2023
Max Planck Institute for Biophysical Chemistry
2011-2022
Center of Molecular Immunology (Cuba)
2009-2016
European Molecular Biology Laboratory
2008
Max Planck Society
2007-2008
The activated spliceosome (B act ) is in a catalytically inactive state and remodeled into active machine by the RNA helicase Prp2, but mechanism unclear. Here, we describe 3D electron cryomicroscopy structure of Saccharomyces cerevisiae B complex at 5.8-angstrom resolution. Our model reveals that , catalytic U2/U6 RNA-Prp8 ribonucleoprotein core already established, 5′ splice site (ss) oriented for step 1 catalysis occluded protein. first-step nucleophile—the branchsite adenosine—is...
Pre-mRNA splicing follows a pathway driven by ATP-dependent RNA helicases. A crucial event of the is catalytic activation, which takes place at transition between activated B
Assembly of a spliceosome, catalyzing precursor–messenger RNA splicing, involves multiple RNA–protein remodeling steps, driven by eight conserved DEXD/H-box helicases. The 250-kDa Brr2 enzyme, which is essential for U4/U6 di-small nuclear ribonucleoprotein disruption during spliceosome catalytic activation and disassembly, the only member this group that permanently associated with thus requiring its faithful regulation. At same time, represents unique subclass superfamily 2 nucleic acid...
Abstract Intron selection during the formation of prespliceosomes is a critical event in pre-mRNA splicing. Chemical modulation intron has emerged as route for cancer therapy. Splicing modulators alter splicing patterns cells by binding to U2 snRNP (small nuclear ribonucleoprotein)—a complex chaperoning branch and 3′ splice sites. Here we report crystal structures SF3B module with spliceostatin sudemycin FR901464 analogs, cryo-electron microscopy structure cross-exon prespliceosome-like...
Abstract Full-length Aβ1-42 and Aβ1-40, N-truncated pyroglutamate Aβ3-42 Aβ4-42 are major variants in the Alzheimer brain. has not been considered as a therapeutic target yet. We demonstrate that antibody NT4X its Fab fragment reacting with both free N-terminus of Aβ4-x Aβ3-X mitigated neuron loss Tg4-42 mice expressing completely rescued spatial reference memory deficits after passive immunization. also working wild type induced by intraventricular injection Aβ4-42. reduced Aβ3-x, Aβx-40...
Abstract Fluorogenic RNA aptamers are synthetic functional RNAs that specifically bind and activate conditional fluorophores. The Chili aptamer mimics large Stokes shift fluorescent proteins exhibits high affinity for 3,5-dimethoxy-4-hydroxybenzylidene imidazolone (DMHBI) derivatives to elicit green or red fluorescence emission. Here, we elucidate the structural mechanistic basis of activation by crystallography time-resolved optical spectroscopy. Two co-crystal structures with positively...
Ferlins, ancient membrane proteins with a unique architecture, are central to multiple essential, Ca 2+ -dependent vesicle fusion processes. Despite numerous functional studies and their link burdening human diseases, mechanistic understanding of how these multi-C 2 domain interact lipid membranes promote remodeling is currently lacking. Here, we elucidate the near-complete cryo-electron microscopy structures myoferlin dysferlin in lipid-bound states. We show that ferlins adopt compact,...
RNA polymerase III (RNAPIII) synthesizes essential and abundant noncoding RNAs such as transfer RNAs. Controlling RNAPIII span of activity by accurate efficient termination is a challenging necessity to ensure robust gene expression prevent conflicts with other DNA-associated machineries. The mechanism believed be simpler than that eukaryotic polymerases, solely relying on the recognition T-tract in nontemplate strand. Here, we combine high-resolution genome-wide analyses vitro transcription...
Cohesin is a protein complex whose core subunits, Smc1, Smc3, Scc1, and SA1/SA2 form ring-like structure encircling the DNA. Cohesins play key role in expression, repair, segregation of eukaryotic genomes. Following catalytic mechanism that insufficiently understood, Esco1 Esco2 acetyltransferases acetylate cohesin subunit thereby inducing stabilization on As prerequisite for structure-guided investigation enzymatic activity, we determine here crystal mouse Esco2/CoA at 1.8 Å resolution. We...
Chromatographic techniques are used in the purification step of human recombinant erythropoietin production process to obtain a reliable product with high purity. Anion-exchange chromatography supports have proved efficient removing contaminants such as DNA. For that reason, DNA removal was determined by spike studies, on three anion-exchange chromatographic supports: gel, membrane, and monolithic column, which is intermediate stage. This study showed membrane monolith columns very good...