A5065973440- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Bacteriophages and microbial interactions
- Antimicrobial Resistance in Staphylococcus
- Bacterial Genetics and Biotechnology
- Advanced Electron Microscopy Techniques and Applications
- Antimicrobial Peptides and Activities
- Toxin Mechanisms and Immunotoxins
- Genomics and Phylogenetic Studies
- Particle accelerators and beam dynamics
- Enzyme Structure and Function
- Poxvirus research and outbreaks
- Nanoparticle-Based Drug Delivery
- RNA Research and Splicing
- Immune Response and Inflammation
- Herpesvirus Infections and Treatments
- Molecular Spectroscopy and Structure
- Peptidase Inhibition and Analysis
- Inorganic Fluorides and Related Compounds
- Medicinal Plants and Bioactive Compounds
- Enterobacteriaceae and Cronobacter Research
- Biological and pharmacological studies of plants
- Glycosylation and Glycoproteins Research
- Freezing and Crystallization Processes
- Advanced Scientific Research Methods
Max Planck Institute of Biophysics
2020-2024
Kazan Federal University
2016-2023
Institut de Biologie Moléculaire et Cellulaire
2015-2022
Institute of Chemical Biology and Fundamental Medicine
2022
Institut de génétique et de biologie moléculaire et cellulaire
2016-2020
Université de Strasbourg
2016-2019
Centre National de la Recherche Scientifique
2016-2019
Inserm
2016-2019
European Molecular Biology Organization
2019
Eurométropole de Strasbourg
2016
Abstract The ribosome, the largest RNA-containing macromolecular machinery in cells, requires metal ions not only to maintain its three-dimensional fold but also perform protein synthesis. Despite vast biochemical data regarding importance of for efficient synthesis and increasing number ribosome structures solved by X-ray crystallography or cryo-electron microscopy, assignment within remains elusive due methodological limitations. Here we present extensive experimental on potassium...
Ribosomes translate genetic information into primary structure. During translation, various cofactors transiently bind to the ribosome that undergoes prominent conformational and structural changes. Different translational states of ribosomes have been well characterized in vitro. However, which extent known are representative native situation inside cells has thus far only addressed prokaryotes. Here, we apply cryo-electron tomography cryo-FIB milled Dictyostelium discoideum combined with...
Ribosomes catalyze protein synthesis by cycling through various functional states. These states have been extensively characterized in vitro, but their distribution actively translating human cells remains elusive. We used a cryo-electron tomography-based approach and resolved ribosome structures inside with high resolution. revealed the of elongation cycle, Z transfer RNA binding site, dynamics expansion segments. Ribosome from treated Homoharringtonine, drug against chronic myeloid...
Abstract Posttranscriptional modifications at the wobble position of transfer RNAs play a substantial role in deciphering degenerate genetic code on ribosome. The number and variety suggest different mechanisms action during messenger RNA decoding, which only few were described so far. Here, basis several 70S ribosome complex X-ray structures, we demonstrate how Escherichia coli tRNA Lys UUU with hypermodified 5-methylaminomethyl-2-thiouridine (mnm 5 s 2 U) discriminates between cognate...
Due to its asymmetric shape, size and compactness, the structure of infectious mature virus (MV) vaccinia (VACV), best-studied poxvirus, remains poorly understood. Instead, subviral particles, in particular membrane-free viral cores, have been studied with cryo-electron microscopy. Here, we compared cores obtained by detergent stripping MVs cellular cytoplasm, early infection. We focused on prominent palisade layer core surface, combining tomography, subtomogram averaging AlphaFold2...
Abstract For the sake of energy preservation, bacteria, upon transition to stationary phase, tone down their protein synthesis. This process is favored by reversible binding small stress-induced proteins ribosome prevent unnecessary translation. One example conserved bacterial silencing factor (RsfS) that binds uL14 onto large ribosomal subunit and prevents its association with subunit. Here we describe mode Staphylococcus aureus RsfS present a 3.2 Å resolution cryo-EM reconstruction...
Abstract Ribosomes translate the genetic code into proteins. Recent technical advances have facilitated in situ structural analyses of ribosome functional states inside eukaryotic cells and minimal bacterium Mycoplasma. However, such Gram-negative bacteria are lacking, despite their ribosomes being major antimicrobial drug targets. Here we compare two E. coli strains, a lab K-12 human gut isolate ED1a, for which tetracycline exhibits bacteriostatic bactericidal action, respectively. Using...
Ribosome biogenesis is a complex and highly accurate conservative process of ribosomal subunit maturation followed by association. Subunit comprises sequential stages RNA proteins' folding, modification binding, with the involvement numerous RNAses, helicases, GTPases, chaperones, RNA, protein-modifying enzymes, assembly factors. One such factor involved in bacterial 30S binding A (RbfA). In this study, we present crystal (determined at 2.2 Å resolution) NMR structures RbfA as well 2.9...
Staphylococcus aureus is a bacterial pathogen and one of the leading causes healthcare-acquired infections in world. The growing antibiotic resistance S. obliges us to search for new drugs treatments. As majority antibiotics target ribosome, knowledge its detailed structure crucial drug development. Here, we report cryo-EM reconstruction at 3.2 Å resolution ribosome with P-site tRNA, messenger RNA, 10 RNA modification sites previously not assigned or visualized. resulting model most precise...
Cryo-electron microscopy is now used as a method of choice in structural biology for studying protein synthesis, process mediated by the ribosome machinery. In order to achieve high-resolution structures using this approach, one needs obtain homogeneous and stable samples, which requires optimization purification species-dependent manner. This especially critical bacterial small ribosomal subunit that tends be unstable absence ligands. Here, we report protocol 30 S from Gram-positive...
Abstract The Rcs signal transduction system is a phosphorelay responsible for sensing wide variety of enterobacterial cell envelope stresses. In Escherichia coli , the required to survive A22 and mecillinam treatment, two drugs that perturb size. To test whether size changes might be correlated with damage thereby sensed by system, we tuned E. via drug inhibition A22, point mutations cell-shape determinant MreB, mechanically confined growth. all conditions, width was strongly activation,...
Abstract Although vaccinia virus (VACV) is the best studied poxvirus, structure of mature (MV) remains poorly understood. Its asymmetric shape, size and compactness poses a major challenge for electron microscopy (EM) analysis, including cryoEM. Sub-viral particles, in particular membrane-free viral cores, may overcome these limitations. We compare cores obtained by detergent-stripping MVs with cellular cytoplasm, early infection. By combining cryo-electron tomography (cryoET), subtomogram...
Abstract Ribosomes catalyze protein synthesis by cycling through various functional states. These states have been extensively characterized in vitro, yet their distribution actively translating human cells remains elusive. Here, we optimized a cryo-electron tomography-based approach and resolved ribosome structures inside with local resolution of up to 2.5 angstroms. revealed the elongation cycle, Z tRNA binding site dynamics expansion segments. In addition, visualized Homoharringtonine,...
SUMMARY Ribosomes translate the genetic code into proteins. Recent technical advances have facilitated in situ structural analyses of ribosome functional states inside eukaryotic cells and minimal bacterium Mycoplasma. However, such Gram-negative bacteria are lacking, despite their ribosomes being major antimicrobial drug targets. Here we compare two E. coli strains, a lab K-12 human gut isolate ED1a, for which tetracycline exhibits bacteriostatic bactericidal action, respectively. The...
Staphylococcus aureus is a major opportunistic and versatile pathogen. Because the bacteria rapidly evolve multi-resistances towards antibiotics, there an urgent need to find novel targets alternative strategies cure bacterial infections. Here, we provide brief overview on knowledge acquired S. ribosomes, which one of antibiotic targets. We will show that subtle differences exist between translation at initiation step Gram-negative Gram-positive although their ribosomes display remarkable...