A5061340516- Microtubule and mitosis dynamics
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Cellular transport and secretion
- Photosynthetic Processes and Mechanisms
- Protist diversity and phylogeny
- Antibiotic Resistance in Bacteria
- RNA and protein synthesis mechanisms
- Escherichia coli research studies
- RNA Interference and Gene Delivery
- Genomics and Phylogenetic Studies
- Microbial Community Ecology and Physiology
- Neurological disorders and treatments
- Probiotics and Fermented Foods
- Infectious Disease Case Reports and Treatments
- Congenital heart defects research
- Ubiquitin and proteasome pathways
- Protein Structure and Dynamics
- Mitochondrial Function and Pathology
- Advanced Electron Microscopy Techniques and Applications
- Actinomycetales infections and treatment
- Drug Transport and Resistance Mechanisms
- Plant Molecular Biology Research
- Infectious Diseases and Mycology
- ATP Synthase and ATPases Research
Imperial College London
2020-2022
Birkbeck, University of London
2017-2020
Institute of Structural and Molecular Biology
2017-2020
Pharmidex (United Kingdom)
2020
Instituto de Biomedicina y Biotecnología de Cantabria
2008-2014
Universidad de Cantabria
2008-2014
Consejo Superior de Investigaciones Científicas
2011-2012
Universitat de les Illes Balears
2012
Hospital del Niño
2008
Abstract Bacterial conjugation mediates contact-dependent transfer of DNA from donor to recipient bacteria, thus facilitating the spread virulence and resistance plasmids. Here we describe how variants plasmid-encoded outer membrane (OM) protein TraN cooperate with distinct OM receptors in recipients mediate mating pair stabilization efficient transfer. We show that plasmid pKpQIL ( Klebsiella pneumoniae ) interacts OmpK36, plasmids R100-1 Shigella flexneri pSLT Salmonella Typhimurium)...
Abstract Flagellar filaments function as the propellers of bacterial flagellum and their supercoiling is key to motility. The outer domains on surface filament are non-critical for motility in many bacteria structures functions not conserved. Here, we show atomic cryo-electron microscopy flagellar from enterohemorrhagic Escherichia coli O157:H7, enteropathogenic E. O127:H6, Achromobacter , Sinorhizobium meliloti where dimerize or tetramerize form either a sheath screw-like surface. These...
VirB4 proteins are ATPases essential for pilus biogenesis and protein transport in type IV secretion systems. These contain a motor domain that shares structural similarities with the domains of DNA translocases, such as VirD4/TrwB conjugative coupling chromosome segregation pump FtsK. Here, we report three-dimensional structure full-length TrwK, homologue plasmid R388, determined by single-particle electron microscopy. The consists hexameric double ring barrel-shaped structure. C-terminal...
Kinesin motors play diverse roles in mitosis and are targets for antimitotic drugs. The clinical significance of these emphasizes the importance understanding molecular basis their function. Equally important, investigations into modes inhibition provide crucial information about mechanisms. Kif18A regulates spindle microtubules through its dual functionality, with microtubule-based stepping regulation microtubule dynamics. We investigated mechanism by small molecule BTB-1. motor domain...
ABSTRACT Type IV secretion systems (T4SS) mediate the transfer of DNA and protein substrates to target cells. TrwK, encoded by conjugative plasmid R388, is a member VirB4 family, comprising largest most conserved proteins T4SS. was suggested be an ATPase involved in energizing pilus assembly substrate transport. However, conflicting experimental evidence concerning ATP hydrolase activity reported. Here, we demonstrate that TrwK able hydrolyze vitro absence its potential macromolecular other...
Kinesin-5 motors are vital mitotic spindle components, and disruption of their function perturbs cell division. We investigated the molecular mechanism human kinesin-5 inhibitor GSK-1, which allosterically promotes tight microtubule binding. GSK-1 inhibits monomeric ATPase gliding activities, motor's stabilization activity. Using cryoelectron microscopy, we determined 3D structure microtubule-bound motor-GSK-1 at 3.8 Å overall resolution. The reveals that stabilizes binding surface motor in...
Pseudomonas stutzeri strain ZoBell, formerly a of perfectomarina (CCUG 16156 = ATCC 14405), is model organism for denitrification. It was isolated by ZoBell in 1944 from marine sample, and here we report the first genome draft assigned to genomovar 2 species P. stutzeri.
Kinesin-5s are microtubule-dependent motors that drive spindle pole separation during mitosis. We used cryo-electron microscopy to determine the 4.5-Å resolution structure of motor domain fission yeast kinesin-5 Cut7 bound microtubules and explored topology motor–microtubule interface susceptibility complex drug binding. Despite their non-canonical architecture mechanochemistry, Schizosaccharomyces pombe were stabilized by epothilone at taxane binding pocket. The overall footprint on S....
Subcellular compartmentalisation is necessary for eukaryotic cell function. Spatial and temporal regulation of kinesin activity essential building these local environments via control intracellular cargo distribution. Kinesin-binding protein (KBP) interacts with a subset kinesins their motor domains, inhibits microtubule (MT) attachment, blocks cellular However, its mechanisms inhibition selectivity have been unclear. Here we use cryo-electron microscopy to reveal the structure KBP...
Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic (EHEC) utilize a macromolecular type III secretion system (T3SS) to inject effector proteins into eukaryotic cells. This apparatus spans the inner outer bacterial membranes includes helical needle protruding extracellular space. Thus far observed only in EPEC EHEC not found other pathogenic Gram-negative bacteria that have T3SS is an additional filament made by EspA protein forms long extension needle, mediating both attachment...
Type IV secretion systems (T4SS) mediate the transfer of DNA and protein substrates to target cells. TrwK, encoded by conjugative plasmid R388, is a member VirB4 family, comprising largest most conserved proteins T4SS. In previous work we demonstrated that TrwK able hydrolyze ATP. Here, based on structural homology with DNA-pumping ATPase TrwB coupling protein, generated series variants where fragments C-terminal domain were sequentially truncated. Surprisingly, in vitro activity these was...
TrwD, the VirB11 homologue in conjugative plasmid R388, is a member of large secretion ATPase superfamily, which includes ATPases from bacterial type II and IV systems, pilus, archaeal flagellae assembly. Based on structural studies homologues Helicobacter pylori Brucella suis GspE, unified mechanism for superfamily has been proposed. Here, we have found that ATP turnover TrwD down-regulated by physiological concentrations magnesium. This regulation exerted increasing affinity ADP, hence...
Nocardia paucivorans brain abscesses are unusual in humans. Sixteen cases of this infection have been reported the world medical literature. There is precise clinical information available from nine patients. All these patients recovered or were cured their disease with long-term antimicrobial treatment. Surgical drainage was performed four
Abstract We investigated the mechanism of conjugal transfer endemic Klebsiella pneumoniae carbapenem resistance plasmid, pKpQIL. Transfer efficiency this plasmid was found to be dependent on expression major outer membrane porin, OmpK36, in recipient cells. also that uptake is reduced recipients expressing an OmpK36 isoform associated with globally pervasive K. ST258 clade (OmpK36 ). This reduction attributed a glycine-aspartate insertion loop 3 , which constricts pore by 26%. Deletion finO...
Summary Kinesin-5s are essential members of the superfamily microtubule-dependent motors that undertake conserved roles in cell division. We investigated coevolution motor-microtubule interface using cryo-electron microscopy to determine near-atomic structure motor domain Cut7, fission yeast kinesin-5, bound microtubules. AMPPNP-bound Cut7 adopts a kinesin-conserved ATP-like conformation, with closed nucleotide binding pocket and docked neck linker supports cover bundle formation. Compared...
Abstract Subcellular compartmentalisation is necessary for eukaryotic cell function. Spatial and temporal regulation of kinesin activity essential building these local environments via control intracellular cargo distribution. Kinesin binding protein (KBP) interacts with a subset kinesins their motor domains, inhibits microtubule (MT) attachment blocks cellular However, its mechanisms inhibition selectivity have been unclear. Here we use cryo-electron microscopy to reveal the structure KBP...