A5015719731- RNA and protein synthesis mechanisms
- Computational Drug Discovery Methods
- Cellular transport and secretion
- RNA modifications and cancer
- Enzyme Structure and Function
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Photochemistry and Electron Transfer Studies
- Luminescence and Fluorescent Materials
- RNA regulation and disease
- Cell Image Analysis Techniques
- Advanced NMR Techniques and Applications
- Calcium signaling and nucleotide metabolism
- COVID-19 Clinical Research Studies
- Mosquito-borne diseases and control
- Selenium in Biological Systems
- Biotin and Related Studies
- RNA Research and Splicing
- Photosynthetic Processes and Mechanisms
- Chemical Synthesis and Analysis
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Advanced Fluorescence Microscopy Techniques
- Metabolomics and Mass Spectrometry Studies
- Insect symbiosis and bacterial influences
Institute for Research in Biomedicine
2020-2025
Institut de Biologia Molecular de Barcelona
2017-2024
Universitat Politècnica de Catalunya
2020
FC Barcelona
2019
Institució Catalana de Recerca i Estudis Avançats
2019
MRC Laboratory of Molecular Biology
2012-2016
Medical Research Council
2015
Institut de Chimie des Substances Naturelles
2009-2010
Centre National de la Recherche Scientifique
2007-2010
Opening up Vps34 protein complexes During intracellular membrane trafficking, large regulate and adapt the activity of signal transducer enzymes such as class III phosphatidylinositol 3-kinase Vps34. These enzyme are present in all eukaryotic cells, having widespread importance neurodegeneration, aging, cancer; however, a structural understanding has been lacking. Rostislavleva et al. provide atomic-resolution insights into structures Vps34-containing required for autophagy, endocytic...
The endosomal sorting complexes required for transport (ESCRTs) facilitate of ubiquitinated cargo, MVB biogenesis, late stages cytokinesis, and retroviral budding. Here we show that ubiquitin associated protein 1 (UBAP1), a subunit human ESCRT-I, coassembles in stable 1:1:1:1 complex with Vps23/TSG101, VPS28, VPS37. X-ray crystal structure the C-terminal region UBAP1 reveals domain describe as solenoid overlapping UBAs (SOUBA). NMR analysis shows each three rigidly arranged making up SOUBA...
The phosphatidylinositol 3-kinase Vps34 is part of several protein complexes. structural organization heterotetrameric complexes starting to emerge, but little known about additional accessory subunits that interact with these assemblies. Combining hydrogen-deuterium exchange mass spectrometry (HDX-MS), X-ray crystallography and electron microscopy (EM), we have characterized Atg38 its human ortholog NRBF2, components complex I consisting Vps15-Vps34-Vps30/Atg6-Atg14 (yeast)...
Variable domains of camelid heavy-chain antibodies, commonly named nanobodies, have high biotechnological potential. In view their broad range applications in research, diagnostics and therapy, engineering stability is particular interest. One important aspect the improvement thermostability, because it can immediate effects on conformational stability, protease resistance aggregation propensity protein. We analyzed sequences thermostabilities 78 purified nanobody binders. From this data,...
ARCIMBOLDO solves the phase problem by combining location of small model fragments using Phaser with density modification and autotracing SHELXE. Mainly helical structures constitute favourable cases, which can be solved polyalanine as search models. Nevertheless, solution coiled-coil is often complicated their anisotropic diffraction apparent translational noncrystallographic symmetry. Long, straight helices have internal symmetry alignment in preferential directions gives rise to...
Zika virus (ZIKV), a member of the Flaviviridae family, has emerged as major public health threat, since ZIKV infection been connected to microcephaly and other neurological disorders. Flavivirus genome replication is driven by NS5, an RNA-dependent RNA polymerase (RdRP) that also contains N-terminal methyltransferase domain essential for viral mRNA capping. Given its crucial roles, NS5 become attractive antiviral target. Here, we have used integrated structural biology approaches...
Abstract An accurate spatial representation of protein-protein interaction networks is needed to achieve a realistic and biologically relevant interactomes. Here, we leveraged the information included in Proximity-Dependent Biotin Identification (BioID) interactomes SARS-CoV-2 proteins calculate weighted distances model organization SARS-CoV-2-human interactome three dimensions (3D) within cell-like volume. Cell regions with viral occupancy were highlighted, along coordination exploiting...
The GTPase Arf1 is the major regulator of vesicle traffic at both cis- and trans-Golgi. activated cis-Golgi by guanine nucleotide exchange factor (GEF) GBF1 trans-Golgi related GEF BIG1 or its paralog, BIG2. trans-Golgi-specific targeting BIG2 depends on Arf-like Arl1. We find that Arl1 binds to dimerization cyclophilin binding (DCB) domain in report a crystal structure human bound this domain. Residues DCB bind are required for locate Golgi vivo. domain-binding residues have distinct...
Designing peptides that fold and assemble in response to metal ions tests our understanding of how peptide folding binding influence one another. Here, histidine residues are introduced into the hydrophobic core a coiled-coil trimer, generating self-assembles upon addition ions. HisAD, resulting peptide, is unstructured absence folds selectively form an α-helical construct complexation with Cu(ii) Ni(ii) but not Co(ii) or Zn(ii). The structure, metal-binding ability, HisAD probed using...
We present a study of the photophysical properties BODIPY-FL fluorescent dye at single molecule scale using total internal reflexion fluorescence microscopy. characterized saturation intensity and maximum number photons for in usual buffer. then studied influence buffer depletion oxygen addition redox agents on brightness lifetime before photobleaching BODIPY-FL. The great improvement these two factors such medium allows use single-molecule biophysics experiments.
Elongation factor SelB is responsible for cotranslational incorporation of the 21(st) amino acid selenocysteine (Sec) into proteins. UGA stop codon recoded as a Sec in presence downstream mRNA hairpin. Prokaryotic has EF-Tu-like N-terminal domains and C-terminal extension containing four tandem winged-helix motifs (WH1-4). The recognizes Crystal structures Escherichia coli WH3/4 WH1-4 from Moorella thermoacetica each bound to were determined. These provide insights how molecular switch that...
Abstract Crystallography at low resolution must determine the atomic model from less experimental observations, which is challenging in absence of a model. In addition, bias more severe when independent data are scarce. Our methods solve phase problem by combining location accurate fragments using Phaser with density modification and interpretation resulting maps SHELXE. From partial, correct structure, process stereochemical constraints draw rest validating result. This same principle now...
Chemical signatures encode the physicochemical and structural properties of small molecules into numerical descriptors, forming basis for chemical comparisons search algorithms. The increasing availability bioactivity data has improved compound representations to include biological effects, although descriptors are often limited a few well-documented molecules. To address this issue, we implemented collection deep neural networks able leverage experimentally determined associated infer...
In bacteria, selenocysteine (the 21st amino acid) is incorporated into proteins via machinery that includes SelB, a specific translational elongation factor. SelB binds to an mRNA hairpin called the selenocysteine-insertion sequence (SECIS) and delivers selenocysteyl-tRNASec ribosomal A site. The minimum C-terminal fragment (residues 478–614) of Escherichia coli (SelB-WH3/4) required for SECIS binding has been overexpressed purified. This protein was crystallized in complex with 23...
We present an online resource, based on small-molecule bioactivity signatures and natural language processing, to expand the portfolio of compounds with potential treat COVID-19. By comparing set drugs reported be potentially active against SARS-CoV-2 a universe 1M bioactive molecules, we identify that display analogous chemical functional features current COVID-19 candidates. Searches can filtered by level evidence mechanism action, results restricted drug molecules or include much broader...
We present an online resource, based on small-molecule bioactivity signatures and natural language processing, to expand the portfolio of compounds with potential treat COVID-19. By comparing set drugs reported be potentially active against SARS-CoV-2 a universe 1M bioactive molecules, we identify that display analogous chemical functional features current COVID-19 candidates. Searches can filtered by level evidence mechanism action, results restricted drug molecules or include much broader...
From a comprehensive proximity-dependent biotinylation (BioID)-based proximal SARS-CoV-2 interactome, we generated 3D map positioning both and host proteins within cell volumes. Then, subset of the proteome to viral polypeptides was probed for direct contacts by semi-quantitative split-nanoluciferase assay. We thus provide an intensity 414 virus-host protein contacts, which 151 involved essential infection. Among 70 complexes modeled AlphaFold2, 10 scored positive, providing as many...