A5081811687- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Antimicrobial Peptides and Activities
- Bacterial Genetics and Biotechnology
- Viral Infections and Immunology Research
- Bacteriophages and microbial interactions
- Biochemical and Structural Characterization
- Genomics and Phylogenetic Studies
- Respiratory viral infections research
- Diagnosis and Treatment of Venous Diseases
- Venous Thromboembolism Diagnosis and Management
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Blood groups and transfusion
- Toxin Mechanisms and Immunotoxins
- Veterinary medicine and infectious diseases
- Chemical synthesis and alkaloids
- Muon and positron interactions and applications
- Microbial Natural Products and Biosynthesis
- Dye analysis and toxicity
- Heat shock proteins research
- Particle accelerators and beam dynamics
- Effects of Radiation Exposure
- Plant Virus Research Studies
- Lung Cancer Diagnosis and Treatment
The University of Texas Medical Branch at Galveston
2018-2024
Yale University
2012-2018
Howard Hughes Medical Institute
2012-2018
Centre Hospitalier de l’Université de Montréal
2015
Université de Montréal
2000-2010
Université du Québec à Montréal
1982
Abstract To conserve energy during starvation and stress, many organisms use hibernation factor proteins to inhibit protein synthesis protect their ribosomes from damage 1,2 . In bacteria, two families of factors have been described, but the low conservation these huge diversity species, habitats environmental stressors confounded discovery 3–6 Here, by combining cryogenic electron microscopy, genetics biochemistry, we identify Balon, a new in cold-adapted bacterium Psychrobacter urativorans...
With bacterial resistance becoming a serious threat to global public health, antimicrobial peptides (AMPs) have become promising area of focus in antibiotic research. AMPs are derived from diverse range species, prokaryotes humans, with mechanism action that often involves disruption the cell membrane. Proline-rich (PrAMPs) instead actively transported inside where they bind and inactivate specific targets. Recently, it was reported some PrAMPs, such as Bac71–35, oncocins apidaecins,...
In bacteria, the hybrid transfer-messenger RNA (tmRNA) rescues ribosomes stalled on defective messenger RNAs (mRNAs). However, certain gram-negative bacteria have evolved proteins that are capable of rescuing in a tmRNA-independent manner. Here, we report 3.2 angstrom-resolution crystal structure rescue factor YaeJ bound to Thermus thermophilus 70S ribosome complex with initiator tRNA(i)(fMet) and short mRNA. The reveals C-terminal tail functions as sensor discriminate between actively...
During stress conditions such as heat shock and antibiotic exposure, ribosomes stall on messenger RNAs, leading to inhibition of protein synthesis. To remobilize ribosomes, bacteria use rescue factors HflXr, a homolog the conserved housekeeping GTPase HflX that catalyzes dissociation translationally inactive into individual subunits. Here we time-resolved cryo-electron microscopy elucidate mechanism ribosome recycling by Listeria monocytogenes HflXr. Within 70S ribosome, HflXr displaces...
Elongation factor 4 (EF4/LepA) is a highly conserved guanosine triphosphatase translation factor. It was shown to promote back-translocation of tRNAs on posttranslocational ribosome complexes and compete with elongation G for interaction pretranslocational ribosomes, inhibiting the phase protein synthesis. Here, we report crystal structure EF4-guanosine diphosphate bound Thermus thermophilus P-site tRNA at 2.9 angstroms resolution. The C-terminal domain EF4 reaches into peptidyl transferase...
Abstract During translation initiation, initiation factor 2 (IF2) holds initiator transfer RNA (fMet-tRNA i fMet ) in a specific orientation the peptidyl (P) site of ribosome. Upon subunit joining IF2 hydrolyzes GTP and, concomitant with inorganic phosphate (P release, changes conformation facilitating fMet-tRNA accommodation into P and transition 70 S ribosome complex (70S-IC) to an elongation-competent The mechanism by which separates from tRNA at end remains elusive. Here, we report...
Aminoglycosides are a class of antibiotics that bind to ribosomal RNA and exert pleiotropic effects on ribosome function. Amikacin, the semisynthetic derivative kanamycin, is commonly used for treating severe infections with multidrug-resistant, aerobic Gram-negative bacteria. Amikacin carries 4-amino-2-hydroxy butyrate (AHB) moiety at N
Significance Many protein factors interact with the ribosome during synthesis. Elongation factor 4 (EF-4/LepA) is a widely distributed and highly conserved translational GTPase for which several physiological roles have been proposed. Despite this, function of EF-4 remains unknown. We determined high-resolution crystal structure bound to in its GTP-bound state A-, P-, E-site tRNAs. Notably, induces distinct conformation tRNA A site, deviates substantially from that canonical A-tRNA....
A new RNA structural motif consisting of two double helices closely packed via minor grooves is found in many places the ribosome structure. The packing requires that a GU base pair one helix be against Watson–Crick other helix. Two such motifs mediate interaction P- and E-tRNA with large ribosomal subunit. Analysis particular positions these view available data on occupancy tRNA-binding sites changes during elongation cycle suggests distinct role for each tRNA translocation.
Here, we present a new recurrent RNA arrangement, the so-called adenosine wedge (A-wedge), which is found in three places of ribosomal both subunits. The arrangement has hierarchical structure, consisting elements previously described as motifs, namely, along-groove packing motif, A-minor and hook-turn. Within A-wedge, these are involved different types cause–effect relationships, providing together for particular tertiary structure motif.
The along-groove packing motif is a quasi-reciprocal arrangement of two RNA double helices in which backbone each helix closely packed within the minor groove other helix. At center inter-helix contact, GU base pair one packs against Watson-Crick Here, based on vivo selection from combinatorial gene library 16 S rRNA and functional characterization selected clones, we demonstrate that normal ribosome performance requires 3 12 be packed. In some clones pairs exchange their positions between...
Abstract Thermorubin (THR) is an aromatic anthracenopyranone antibiotic active against both Gram-positive and Gram-negative bacteria. It known to bind the 70S ribosome at intersubunit bridge B2a was thought inhibit factor-dependent initiation of translation obstruct accommodation tRNAs into A site. Here, we show that thermorubin causes ribosomes stall in vivo vitro internal termination codons, thereby allowing initiate protein synthesis translate least a few codons before stalling. Our...
Bacterial ribosomal protein S7 initiates the folding of 3′ major domain 16S RNA by binding to its lower half. The X-ray structure from thermophilic bacteria was recently solved and found be a modular structure, consisting an α-helical with β-ribbon extension. To gain further insights into interaction rRNA, we cloned gene Escherichia coli K12 pET expression vector introduced 4 deletions 12 amino acid substitutions in sequence. each mutant half rRNA assessed filtration on nitrocellulose...
Respiratory syncytial virus (RSV), along with other prominent respiratory RNA viruses such as influenza and SARS-CoV-2, significantly contributes to the global incidence of tract infections. These pathogens induce production reactive oxygen species (ROS), which play a crucial role in onset progression diseases. However, mechanisms by viral manages ROS-induced base oxidation remain poorly understood. Here, we reveal that 8-oxo-7,8-dihydroguanine (8-oxoGua) is not merely an incidental...
To understand how the nucleotide sequence of ribosomal RNA determines its tertiary structure, we developed a new approach for identification those features rRNA that are responsible formation different short- and long-range interactions. The is based on co-analysis several examples particular recurrent motif. For cases motif, design combinatorial gene libraries in which equivalent positions randomized. Through vivo expression designed select variants provide functional ribosomes. Then,...