A5048297384- Enzyme Structure and Function
- Protein Structure and Dynamics
- Advanced X-ray Imaging Techniques
- Inorganic Chemistry and Materials
- Photoreceptor and optogenetics research
- Iron-based superconductors research
- X-ray Spectroscopy and Fluorescence Analysis
- Rare-earth and actinide compounds
- Mass Spectrometry Techniques and Applications
- RNA and protein synthesis mechanisms
- Photosynthetic Processes and Mechanisms
- Advanced Electron Microscopy Techniques and Applications
- Biochemical and Molecular Research
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Computational Drug Discovery Methods
- Bacterial Genetics and Biotechnology
- Crystallization and Solubility Studies
- Crystal Structures and Properties
- Glycosylation and Glycoproteins Research
- Viral Infections and Immunology Research
- SARS-CoV-2 and COVID-19 Research
- Medical Imaging Techniques and Applications
- Neuroscience and Neuropharmacology Research
- Hepatitis C virus research
Paul Scherrer Institute
2016-2025
Swiss Light Source
2008-2022
European Synchrotron Radiation Facility
2021
Institut de Biologie Structurale
2009-2021
Max Planck Institute for Marine Microbiology
2021
Université Grenoble Alpes
2009-2021
CEA Grenoble
2021
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2021
Centre National de la Recherche Scientifique
2021
Shandong University
2011-2020
The pandemic of coronavirus disease 2019 (COVID-19) is changing the world like never before. This crisis unlikely contained in absence effective therapeutics or vaccine. papain-like protease (PLpro) severe acute respiratory syndrome 2 (SARS-CoV-2) plays essential roles virus replication and immune evasion, presenting a charming drug target. Given PLpro proteases SARS-CoV-2 SARS-CoV share significant homology, inhibitor developed for promising starting point therapeutic development. In this...
Abstract Historically, room-temperature structure determination was succeeded by cryo-crystallography to mitigate radiation damage. Here, we demonstrate that serial millisecond crystallography at a synchrotron beamline equipped with high-viscosity injector and high frame-rate detector allows typical crystallographic experiments be performed room-temperature. Using crystal scanning approach, determine the high-resolution of sensitive molybdenum storage protein, soaking drug colchicine into...
Recent advances in synchrotron sources, beamline optics and detectors are driving a renaissance room-temperature data collection. The underlying impetus is the recognition that conformational differences observed functionally important regions of structures determined using crystals kept at ambient as opposed to cryogenic temperature during In addition, measurements enable time-resolved studies eliminate need find suitable cryoprotectants. Since radiation damage limits high-resolution can be...
Refilling the proton pump Proteins are dynamic. Rearrangements of side chains, secondary structure, and entire domains gate functional transitions on time scales ranging from picoseconds to milliseconds. Weinert et al. used time-resolved serial crystallography study large conformational changes in bacteriorhodopsin that allow for redistribution protons during pumping cycle. They adapted methods x-ray free electron lasers synchrotron sources. Large loop movements a chain water molecules were...
Abstract Although the accessory proteins are considered non-essential for coronavirus replication, accumulating evidences demonstrate they critical to virus-host interaction and pathogenesis. Orf9b is a unique protein of SARS-CoV-2 SARS-CoV. It implicated in immune evasion by targeting mitochondria, where it associates with versatile adapter TOM70. Here, we determined crystal structure orf9b complex cytosolic segment human TOM70 2.2 Å. A central portion occupies deep pocket C-terminal domain...
Chloride transport by microbial rhodopsins is an essential process for which molecular details such as the mechanisms that convert light energy to drive ion pumping and ensure unidirectionality of have remained elusive. We combined time-resolved serial crystallography with spectroscopy multiscale simulations elucidate mechanism a chloride-pumping rhodopsin structural dynamics throughout cycle. traced transient anion-binding sites, obtained evidence how used in mechanism, identified steric...
Middle East respiratory syndrome coronavirus (MERS-CoV) remains a threat to public health worldwide; however, effective vaccine or drug against CoVs unavailable. CoV helicase is one of the three evolutionary most conserved proteins in nidoviruses, thus making it an important target for development. We report here first structure full-length helicase, MERS-CoV nsp13. has multiple domains, including N-terminal Cys/His rich domain (CH) with zinc atoms, beta-barrel and C-terminal SF1 core two...
The development of single-photon-counting detectors, such as the PILATUS, has been a major recent breakthrough in macromolecular crystallography, enabling noise-free detection and novel data-acquisition modes. new EIGER detector features pixel size 75 × µm, frame rates up to 3000 Hz dead time low 3.8 µs. An 1M 16M were tested on Swiss Light Source beamlines X10SA X06SA for their application crystallography. combination fast very short allows high-quality data acquisition shorter time....
The lipid cubic phase (LCP) continues to grow in popularity as a medium which generate crystals of membrane (and soluble) proteins for high-resolution X-ray crystallographic structure determination. To date, the PDB includes 227 records attributed LCP or meso method. Among listings are some highest profile proteins, including β2-adrenoreceptor-Gs protein complex that figured award 2012 Nobel Prize Chemistry Lefkowitz and Kobilka. most successful protocol date uses glass sandwich...
Here, a method for presenting crystals of soluble and membrane proteins growing in the lipid cubic or sponge phase situ diffraction data collection at cryogenic temperatures is introduced. The dispenses with need technically demanding inefficient crystal-harvesting step that an integral part meso crystals. Crystals are dispersed bolus mesophase sandwiched between thin plastic windows. contains tens to hundreds crystals, visible in-line microscope macromolecular crystallography synchrotron...
Abstract Background The therapeutic potential of mesenchymal stem cells (MSCs) may be attributed partly to the secreted paracrine factors, which comprise exosomes. Exosomes are small, saucer-shaped vesicles containing miRNAs, mRNAs, and proteins. derived from human umbilical cord (hUC-MSCs) have been reported promote angiogenesis. However, efficacy exosome-based therapies is still limited both in vitro vivo. present study aimed develop a new optical manipulation approach stimulate...
The binding and release of ligands from their protein targets is central to fundamental biological processes as well drug discovery. Photopharmacology introduces chemical triggers that allow the changing ligand affinities thus activity by light. Insight into molecular mechanisms photopharmacology largely missing because relevant transitions during light-triggered reaction cannot be resolved conventional structural biology. Using time-resolved serial crystallography at a synchrotron X-ray...
The multicopper oxidase phenoxazinone synthase (PHS) catalyzes the penultimate step in biosynthesis of antibiotic actinomycin D by Streptomyces antibioticus. PHS exists two oligomeric forms: a dimeric form and hexameric form, with older actinomycin-producing cultures containing predominately form. structure has been determined using X-ray diffraction to resolution limit 2.30 Å is found contain several unexpected distinctive features. forms ring that centered on pseudo 6-fold axis an outer...
The data-collection parameters used in a macromolecular diffraction experiment have strong impact on data quality. A careful choice of leads to better and can make the difference between success failure phasing attempts, will also result more accurate atomic model. selection has account for application various methods or high-resolution refinement. Furthermore, experimental factors such as crystal characteristics, available time properties X-ray source detector be considered. For many years,...
EV71 is the primary pathogenic cause of hand-foot-mouth disease (HFMD), but an effective antiviral drug currently unavailable. Rupintrivir, inhibitor against human rhinovirus (HRV), has potent activities EV71. We determined high-resolution crystal structures 3C(pro)/rupintrivir complex, showing that although rupintrivir interacts with 3C(pro) similarly to HRV 3C(pro), C terminus cannot accommodate leaving-group pockets 3C(pro). Our reveal possesses a surface-recessive S2' pocket not present...
Significance ABC transporters shuttle chemically diverse substances across membranes in an energy-dependent manner. They mediate multidrug resistance microorganisms and cancer cells can cause human pathologies when dysfunctional. Although important insights into have been gained recent years, fundamental questions concerning their mechanism remain open. Here, we identify the protein complex TmrAB as a functional homolog of antigenic peptide transporter TAP present its high-resolution...
Abstract Human coronavirus (CoV) HKU1 is a pathogen causing acute respiratory illnesses and so far little known about its biology. virus uses S1 subunit C-terminal domain (CTD) not the N-terminal like other lineage A β-CoVs to bind yet unknown human receptor. Here we present crystal structure of CTD at 1.9 Å resolution. The consists three subdomains: core, insertion subdomain-1 (SD-1). While core SD-1 subdomains are highly similar those β-CoVs, subdomain adopts novel fold, which largely...
Abstract 5-hydroxytryptamine (5-HT, also known as serotonin) regulates many physiological processes through the 5-HT receptor family. Here we report crystal structure of 1B subtype (5-HT R) bound to psychotropic serotonin inverse agonist methiothepin (MT). Crystallization was facilitated by replacing ICL3 with a novel optimized variant BRIL (OB1) that enhances formation intermolecular polar interactions, making OB1 potential useful tool for structural studies membrane proteins. Unlike...