A5059939534- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- RNA regulation and disease
- Health and Medical Research Impacts
- Genetics, Bioinformatics, and Biomedical Research
- Cancer-related molecular mechanisms research
- Genomics and Phylogenetic Studies
- CRISPR and Genetic Engineering
- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- Bacterial Genetics and Biotechnology
- Molecular Biology Techniques and Applications
- PI3K/AKT/mTOR signaling in cancer
- Chemical Synthesis and Analysis
- Plant Virus Research Studies
- Viral Infections and Immunology Research
- Biochemical and Molecular Research
- Biomedical and Engineering Education
- Cancer-related gene regulation
- Biotin and Related Studies
- Enzyme Catalysis and Immobilization
- Click Chemistry and Applications
- Diversity and Career in Medicine
- Bacteriophages and microbial interactions
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2014-2024
National Institutes of Health
2014-2024
National Institute of General Medical Sciences
2014-2024
University of California, Berkeley
2020
Johns Hopkins University
2006-2015
Johns Hopkins Medicine
2005-2014
Institute of Molecular Biology and Biophysics
2014
Shoolini University
2014
Swarthmore College
2012
Balboa Nephrology Medical Group
2008
Highlights•Structure of a partial yeast 48S translation initiation complex at 4.0 Å resolution•A distorted initiator tRNA is trapped in the act recognizing start codon•The codon-anticodon duplex stabilized by N-terminal tail eIF1A•eIF2α makes contacts with key nucleotides −2 and −3 positions mRNASummaryDuring eukaryotic initiation, does not insert fully into P decoding site on 40S ribosomal subunit. This conformation (POUT) compatible scanning mRNA for AUG codon. Base pairing thought to...
eIF4A is the archetypal member of DEAD box family proteins and has been proposed to use energy from ATP hydrolysis unwind structures in 5'-untranslated regions eukaryotic mRNAs during translation initiation. As a step toward understanding mechanism action this class enzymes, minimal kinetic thermodynamic framework for RNA-activated ATPase function established eIF4A. The enzyme's affinity ssRNA modulated by binding ATP·Mg2+ ADP·Mg2+: E·ATP complex approximately 40-fold higher than that E·ADP...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIn vitro selection of RNA aptamers specific for cyanocobalaminJon R. Lorsch and Jack W. SzostakCite this: Biochemistry 1994, 33, 4, 973–982Publication Date (Print):February 1, 1994Publication History Published online1 May 2002Published inissue 1 February 1994https://pubs.acs.org/doi/10.1021/bi00170a016https://doi.org/10.1021/bi00170a016research-articleACS PublicationsRequest reuse permissionsArticle Views1578Altmetric-Citations158LEARN ABOUT THESE...
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Selection of the AUG start codon is a key step in translation initiation requiring hydrolysis GTP eIF2•GTP•Met-tRNA i Met ternary complex (TC) and subsequent P release from eIF2•GDP•P . It thought that eIF1 prevents recognition non-AUGs by promoting scanning blocking at non-AUG codons. We show Sui − mutations Saccharomyces cerevisiae eIF1, which increase UUG codons, reduce interaction with 40S subunits vitro vivo, both defects are diminished cells overexpressing mutant proteins. Remarkably,...
The last step in eukaryotic translational initiation involves the joining of large and small subunits ribosome, with initiator transfer RNA (Met-tRNA(i)(Met)) positioned over start codon messenger P site. This is catalyzed by factor eIF5B. We used recent advances cryo-electron microscopy (cryo-EM) to determine a structure eIF5B complex 6.6 angstrom resolution from <3% population, comprising just 5143 particles. reveals conformational changes eIF5B, tRNA, ribosome that provide insights into...
Organizing and accessing biomedical big data will require quite different business models, say Philip E. Bourne, Jon R. Lorsch Eric D. Green.
In eukaryotic translation initiation, AUG recognition of the mRNA requires accommodation Met-tRNAi in a 'PIN' state, which is antagonized by factor eIF1. eIF5 GTPase activating protein (GAP) eIF2 that additionally promotes stringent selection, but molecular basis its dual function was unknown. We present cryo-electron microscopy (cryo-EM) reconstruction yeast 48S pre-initiation complex (PIC), at an overall resolution 3.0 Å, featuring N-terminal domain (NTD) bound to 40S subunit location...
The translation pre-initiation complex (PIC) scans the mRNA for an AUG codon in favorable context, and recognition stabilizes a closed PIC conformation. unstructured N-terminal tail (NTT) of yeast eIF1A deploys five basic residues to contact tRNAi, mRNA, or 18S rRNA exclusively state. Interestingly, EIF1AX mutations altering human NTT are associated with uveal melanoma (UM). We found that substituting all residues, seven UM-associated substitutions, suppresses initiation at near-cognate UUG...
Biomedical data are growing exponentially in both volume and levels of complexity, due to the rapid advancement technologies research methodologies. Analyzing these large datasets, referred collectively as "big data," has become an integral component that guides experimentation-driven discovery a new engine itself it uncovers previously unknown connections through mining existing data. To fully realize potential big data, biomedical researchers need access high-performance-computing (HPC)...
Limited proteolysis experiments have been carried out with the DEAD box protein eIF4A. The results suggest that there is a substantial conformational change in eIF4A upon binding single-stranded RNA. Binding of ADP induces changes free enzyme and enzyme·RNA complex, ATP analogue AMP−PNP complex. presence or absence γ-phosphate on bound nucleotide acts as switch, presumably via Walker motifs, mediates conformation and, described preceding paper this issue, also RNA affinity. Thus, these...