A5054593897- Immune Response and Inflammation
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Influenza Virus Research Studies
- Escherichia coli research studies
- Antimicrobial Peptides and Activities
- Peptidase Inhibition and Analysis
- RNA Research and Splicing
- Advanced Electron Microscopy Techniques and Applications
- Advanced biosensing and bioanalysis techniques
- Genetics and Neurodevelopmental Disorders
- Immunodeficiency and Autoimmune Disorders
- Immune Cell Function and Interaction
- Blood disorders and treatments
- Bacteriophages and microbial interactions
- NF-κB Signaling Pathways
- Heme Oxygenase-1 and Carbon Monoxide
- Cystic Fibrosis Research Advances
- Porphyrin Metabolism and Disorders
- Neonatal Health and Biochemistry
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neonatal Respiratory Health Research
- Physics of Superconductivity and Magnetism
- Monoclonal and Polyclonal Antibodies Research
- Particle accelerators and beam dynamics
University of Cambridge
2019-2024
Medical Research Council
2019-2021
Wellcome Trust
2018-2021
Stem Cell Institute
2019-2021
Institute for Medical Research
2019-2021
Wellcome/MRC Cambridge Stem Cell Institute
2019
Bioinformatics Institute
2015-2018
Agency for Science, Technology and Research
2015-2018
University of Manchester
2015-2018
Genomics (United Kingdom)
2017
Abstract Indirect somatic genetic rescue (SGR) of a germline mutation is thought to be rare in inherited Mendelian disorders. Here, we establish that acquired mutations the EIF6 gene are frequent mechanism SGR Shwachman-Diamond syndrome (SDS), leukemia predisposition disorder caused by defect ribosome assembly. Biallelic SBDS or EFL1 genes SDS impair release anti-association factor eIF6 from 60S ribosomal subunit, key step translational activation ribosomes. identify diverse mosaic events...
During their final maturation in the cytoplasm, pre-60S ribosomal particles are converted to translation-competent large subunits. Here, we present mechanism of peptidyltransferase centre (PTC) completion that explains how integration last proteins is coupled release nuclear export adaptor Nmd3. Single-particle cryo-EM reveals eL40 recruitment stabilises helix 89 form uL16 binding site. The loading unhooks 38 from Nmd3 adopt its mature conformation. In turn, partial retraction L1 stalk a...
Abstract Hereditary porphyrias are caused by mutations in genes that encode haem biosynthetic enzymes with resultant buildup of cytotoxic metabolic porphyrin intermediates. A long-standing open question is why the same causal porphyria exhibit widely variable penetrance and expressivity different individuals. Here we show severely affected patients harbour variant alleles ABCB6 gene, also known as Lan , which encodes an ATP-binding cassette (ABC) transporter. Plasma membrane exports a...
Wzz is an integral inner membrane protein involved in regulating the length of lipopolysaccharide O-antigen glycans and essential for virulence many Gram-negative pathogens. In all homologs, large periplasmic domain proposed to be anchored by two transmembrane helices, but no information available cytosolic domains. Here we have studied purified oligomeric complexes using cryoelectron microscopy resolved regions within a semi-continuous detergent micelle. The helices each monomer display...
Abstract Myosin motors perform many fundamental functions in eukaryotic cells by providing force generation, transport or tethering capacity. Motor activity control within the cell involves on/off switches, however, few examples are known of how myosins regulate speed processivity and fine-tune their to a specific cellular task. Here, we describe phosphorylation event for class VI (MYO6) motor domain, which accelerates its ATPase leading 4-fold increase determined actin-gliding assays,...
Abstract The AAA-ATPase Drg1 is a key factor in eukaryotic ribosome biogenesis that initiates cytoplasmic maturation of the large ribosomal subunit. releases shuttling Rlp24 from pre-60S particles shortly after nuclear export, strict requirement for downstream maturation. molecular mechanism release remained elusive. Here, we report series cryo-EM structures captured extraction by Saccharomyces cerevisiae Drg1. These reveal Arx1 and eukaryote-specific rRNA expansion segment ES27 form joint...