A5020973644- Bacteriophages and microbial interactions
- Viral Infections and Vectors
- RNA and protein synthesis mechanisms
- Neuroscience and Neuropharmacology Research
- Mosquito-borne diseases and control
- Plant Virus Research Studies
- Animal Disease Management and Epidemiology
- Plant and Fungal Interactions Research
- Receptor Mechanisms and Signaling
- Viral Infections and Immunology Research
- Advanced Electron Microscopy Techniques and Applications
- Chemical Synthesis and Analysis
- Enzyme Structure and Function
- Cytomegalovirus and herpesvirus research
- Herpesvirus Infections and Treatments
- Viral gastroenteritis research and epidemiology
- Microtubule and mitosis dynamics
- RNA modifications and cancer
- Solid-state spectroscopy and crystallography
- Vector-Borne Animal Diseases
- thermodynamics and calorimetric analyses
- Molecular spectroscopy and chirality
- Supramolecular Self-Assembly in Materials
- Innovative Microfluidic and Catalytic Techniques Innovation
- Analytical Chemistry and Chromatography
New York Structural Biology Center
2022-2024
Simons Foundation
2022-2024
Centre for Human Genetics
2015-2021
University of Oxford
2015-2021
Electron cryomicroscopy can yield near-atomic resolution structures of highly ordered macromolecular complexes. Often however some subunits bind in a flexible manner, have different symmetry from the rest complex, or are present sub-stoichiometric amounts, limiting attainable resolution. Here we report general method for localized three-dimensional reconstruction such subunits. After determining particle orientations, local areas corresponding to be extracted and treated as single particles....
Abstract Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine–glycine–aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1. Infection can also occur tissue culture adapted absence acquired basic mutations interacting with heparin sulphate (HS); this is attenuated natural infections. HS interaction has been visualized at site two serotypes suggesting propensity for sulfated-sugar...
Abstract Flaviviruses such as Dengue (DENV) or Zika virus (ZIKV) assemble into an immature form within the endoplasmatic reticulum (ER), and are then processed by furin protease in trans-Golgi. To better grasp maturation, we carry out cryo-EM reconstructions of Spondweni (SPOV), a human flavivirus same serogroup ZIKV. By employing asymmetric localised reconstruction push resolution to 3.8 Å, enabling us refine atomic model which includes crucial recognition site conserved Histidine...
Glycine Receptors (GlyRs) provide inhibitory neuronal input in the spinal cord and brainstem, which is critical for muscle coordination sensory perception. Synaptic GlyRs are a heteromeric assembly of α β subunits. Here we present cryo-EM structures full-length zebrafish α1βBGlyR presence an antagonist (strychnine), agonist (glycine), or with positive allosteric modulator (glycine/ivermectin). Each structure shows distinct pore conformation varying degrees asymmetry. Molecular dynamic...
Abstract Correct outer protein shell assembly is a prerequisite for virion infectivity in many multi-shelled dsRNA viruses. In the prototypic bacteriophage φ6, reaction promoted by calcium ions but its biomechanics remain poorly understood. Here, we describe near-atomic resolution structure of φ6 double-shelled particle. The T =13 P8 consists two alpha-helical domains joined linker, which allows trimer to adopt either closed or an open conformation. trimers conformation swap with each other....
Abstract Many of the largest known viruses belong to PRD1-adeno structural lineage characterised by conserved pseudo-hexameric capsomers composed three copies a single major capsid protein (MCP). Here, high-resolution cryo-EM analysis, we show that class archaeal possess hetero-hexameric MCPs which mimic trimer. These hetero-hexamers are built from heterodimers and utilise jigsaw-puzzle system pegs holes, underlying minor proteins, assemble laterally 5-fold vertices. At these vertices...
Foot-and-mouth disease virus (FMDV) is highly contagious and infects cloven-hoofed domestic livestock leading to foot-and-mouth (FMD). FMD outbreaks have severe economic impact due production losses associated control measures. FMDV found as seven distinct serotypes, but there are numerous subtypes within each serotype, effective vaccines must match the circulating in field. In addition, O Southern African Territories (SAT) relatively more thermolabile their viral capsids readily dissociate...
Double-stranded RNA viruses infect a wide spectrum of hosts, including animals, plants, fungi, and bacteria. Yet genome replication mechanisms these are conserved. During the infection cycle, proteinaceous capsid, polymerase complex, is formed. An essential component this capsid viral that replicates transcribes enclosed genome. The complex structure well characterized for many double-stranded viruses. However, much less known about hierarchical molecular interactions take place in building...
Abstract Mosquito-transmitted flaviviruses, such as Dengue virus (DENV) or Zika (ZIKV), are responsible for significant economic damage and human misery. In infected cells, flaviviruses first assemble into an immature form within the endoplasmatic reticulum (ER), then undergo further processing by furin protease in trans-Golgi. Despite substantial efforts, previous cryogenic electron microscopy (cryo-EM) studies of were restricted to low medium resolutions, limiting our understanding...