A5037535731- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- HIV Research and Treatment
- interferon and immune responses
- Herpesvirus Infections and Treatments
- Bacterial Genetics and Biotechnology
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- Bacteriophages and microbial interactions
- Genomics and Chromatin Dynamics
- Magnetic and transport properties of perovskites and related materials
- Fungal Infections and Studies
- Virology and Viral Diseases
- Cytomegalovirus and herpesvirus research
- Influenza Virus Research Studies
- PARP inhibition in cancer therapy
- Magnetic Properties of Alloys
- Protein Structure and Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Rare-earth and actinide compounds
- Viral Infections and Immunology Research
MRC Laboratory of Molecular Biology
2018-2023
University of Utah
2008-2016
Highlights•ZNF598 is a direct sensor of ribosome collisions incurred by many unrelated causes•The minimal target recognized and ubiquitinated ZNF598 collided di-ribosome•Collided di-ribosome structure shows that ubiquitin sites are near the interface•Collisions required to terminally arrest translation in ZNF598-dependent mannerSummaryAberrantly slow elicits quality control pathways initiated ligase ZNF598. How discriminates physiologic from pathologic complexes ubiquitinates stalled...
The nascent polypeptide–associated complex (NAC) interacts with newly synthesized proteins at the ribosomal tunnel exit and competes signal recognition particle (SRP) to prevent mistargeting of cytosolic mitochondrial polypeptides endoplasmic reticulum (ER). How NAC antagonizes SRP how this is overcome by ER targeting signals are unknown. Here, we found that uses two domains opposing effects control access. core globular domain prevented from binding signal-less ribosomes, whereas a flexibly...
TRIM5α proteins are restriction factors that protect mammalian cells from retroviral infections by binding incoming viral capsids, accelerating their dissociation, and preventing reverse transcription of the genome. Individual TRIM5 isoforms can often against a broad range retroviruses, as exemplified rhesus monkey its variant, TRIM5-21R, which recognize HIV-1 well several distantly related retroviruses. Although capsid recognition is not yet fully understood, previous work has shown...
Significance Tripartite motif or TRIM proteins make up the largest superfamily of RING-domain E3 ubiquitin ligases. These enzymes function in a wide variety important cellular processes, particularly innate antiviral response mechanisms. Dimerization is critical for many proteins. Here we show how TRIM25 dimerizes and demonstrate that this dimerization mode apparently conserved across entire protein family. Our results reveal domain positions other effector domains to recognize ubiquitylate...
Tubulins play crucial roles in cell division, intracellular traffic, and shape. Tubulin concentration is autoregulated by feedback control of messenger RNA (mRNA) degradation via an unknown mechanism. We identified tetratricopeptide protein 5 (TTC5) as a tubulin-specific ribosome-associating factor that triggers cotranslational tubulin mRNAs response to excess soluble tubulin. Structural analysis revealed TTC5 binds near the ribosome exit tunnel engages amino terminus nascent tubulins....
TRIM5 proteins are restriction factors that block retroviral infections by binding viral capsids and preventing reverse transcription. Capsid recognition is mediated C-terminal domains on TRIM5α (SPRY) or TRIMCyp (cyclophilin A), which interact weakly with capsids. Efficient capsid also requires the conserved N-terminal tripartite motifs (TRIM), mediate oligomerization create avidity effects. To characterize how recognize capsids, we developed methods for isolating native recombinant...
Quality control in mitochondria Human have their own genome and ribosomes called mitoribosomes that respectively encode synthesize essential subunits of complexes use the energy from oxidation metabolites to drive synthesis adenosine triphosphate (ATP). These are key health cell. Desai et al. studied a mitoribosome-associated quality pathway prevents aberrant translation. They purified under conditions designed induce stalling determined structures two intermediates rescue pathway. revealed...
The rhesus monkey intrinsic immunity factor TRIM5alpha(rh) recognizes incoming capsids from a variety of retroviruses, including human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia (EIAV), inhibits the accumulation viral reverse transcripts. However, direct interactions between restricting TRIM5alpha proteins retroviral have not previously been demonstrated using pure recombinant proteins. To facilitate structural mechanistic studies restriction, we developed methods for...
Ribosome assembly is an essential and conserved process that regulated at each step by specific factors. Using cryo-electron microscopy (cryo-EM), we visualize the formation of peptidyl transferase center (PTC) human mitochondrial ribosome. The GTPase GTPBP7 regulates correct folding 16S ribosomal RNA (rRNA) helices ensures 2ʹ-O-methylation PTC base U3039. binds methyltransferase NSUN4 MTERF4, which sequester H68-71 rRNA allow biogenesis factors to access maturing PTC. Mutations disrupt...
Abstract Eukaryotic messenger RNA (mRNA) decay is generally initiated by removal of the 3’ polyadenosine (poly(A)) tail CCR4-NOT complex. Yeast Ccr4-Not binds and ubiquitinates ribosomes stalled on mRNAs with sub-optimal codons to trigger deadenylation associated transcript. However, mammalian ortholog E3 ubiquitin ligase subunit, CNOT4, not a constitutive component human CCR4-NOT. It therefore remains unclear how machinery targets ribosomes. Here, we reconstitute translational stalling...
Summary Ribosome assembly is an essential and complex process that regulated at each step by specific biogenesis factors. Using cryo-electron microscopy, we identify order major steps in the formation of highly conserved peptidyl transferase centre (PTC) tRNA binding sites large subunit human mitochondrial ribosome (mitoribosome). The GTPase GTPBP7 regulates folding incorporation core 16S ribosomal RNA (rRNA) helices protein bL36m, ensures PTC base U3039 has been 2′-O-methylated....
Hierarchical assembly of colloidal Sm2Co7/Co clusters in the form nanospheres has been processed through a polyol process. The SmCo are found to be robust, uniform ( 100 nm) and tend self-assemble ordered superstructures. Each nanosphere consists large number discrete fine particles 6.0 nm), having two-phase structure both Sm2Co7 Co-phases. Upon annealing, these phases transform into Sm2Co17 phase with very high magnetization (169 emu/g). A possible mechanism on formation from individual...
Mammalian hosts have evolved protein restriction factors to combat retroviruses. TRIM5α and the related TRIMCyp (collectively TRIM5), are that can potently restrict retroviruses, including HIV-1, by binding their capsids blocking reverse transcription. Previous studies shown C-terminal SPRY/CypA domains of TRIM5 proteins bind susceptible retroviruses higher-order oligomerization apparently also contributes capsid binding. However, biochemical structural details these interactions not fully...
Journal Article Mechanism of Signal Sequence Handover From NAC To SRP on Ribosomes During ER-protein Targeting Get access Ahmad Jomaa, Jomaa Department Biology, Institute Molecular Biology and Biophysics, ETH Zurich, Switzerland Search for other works by this author on: Oxford Academic Google Scholar Martin Gamerdinger, Gamerdinger Microbiology, University Konstanz, Germany Hao-Hsuan Hsieh, Hsieh Division Chemistry Chemical Engineering, California Technology, Pasadena, CA, USA Annalena...