Searching across hundreds of databases
Double-stranded RNA (dsRNA) is a potent proinflammatory signature of viral infection. Long cytosolic dsRNA is recognized by MDA5. The cooperative assembly of MDA5 into helical filaments on dsRNA nucleates the assembly of a multiprotein type I interferon signaling platform. Here, we determined cryoelectron microscopy (cryo-EM) structures of MDA5-dsRNA filaments with different helical twists and bound nucleotide analogs at resolutions sufficient to build and refine atomic models. The structures identify the filament-forming interfaces, which encode the dsRNA binding cooperativity and length specificity of MDA5. The predominantly hydrophobic interface contacts confer flexibility, reflected in the variable helical twist within filaments. Mutation of filament-forming residues can result in loss or gain of signaling activity. Each MDA5 molecule spans 14 or 15 RNA base pairs, depending on the twist. Variations in twist also correlate with variations in the occupancy and type of nucleotide in the active site, providing insights on how ATP hydrolysis contributes to MDA5-dsRNA recognition.
Pubmed ID: 30449722 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
The MRC Laboratory of Molecular Biology (LMB) has long been, and remains, a world-class research laboratory. Our primary goal is to understand biological processes at the molecular level, through the application of methods drawn from physics, chemistry and genetics. This quest extends from structural studies of individual macromolecules, through their interactions and beyond to the functioning of subcellular systems, cells and multicellular systems in whole organisms, with the ultimate aim of using this knowledge to tackle specific problems in human health and disease. The LMB is one of the birthplaces of modern molecular biology. Many techniques were pioneered at the laboratory, most notably methods for determining the three-dimensional structure of proteins and DNA sequencing. Whole genome sequencing was initiated at the LMB. Another landmark discovery was the invention of monoclonal antibodies. Over the years, the work of LMB scientists has attracted 9 Nobel Prizes, shared between 13 LMB scientists, as well as numerous other prizes and scientific awards.
View all literature mentionsA commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.
View all literature mentionsA structure-validation web application which provides an expert-system consultation about the accuracy of a macromolecular structure model, diagnosing local problems and enabling their correction. MolProbity works best as an active validation tool (used as soon as a model is available and during each rebuild/refine loop) and when used for protein and RNA crystal structures, but it may also work well for DNA, ligands and NMR ensembles. It produces coordinates, graphics, and numerical evaluations that integrate with either manual or automated use in systems such as PHENIX, KiNG, or Coot.
View all literature mentionsSoftware tool for anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Used to describe the sample motion as a local deformation that varies smoothly throughout the exposure. A program running on Linux.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Actin antibody [AC-40]
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsA Python-based software suite for the automated determination of molecular structures using X-ray crystallography and other methods. Phenix includes programs for assessing data quality, experimental phasing, molecular replacement, model building, structure refinement, and validation. It also includes tools for reflection data and creating maps and models. Phenix can also be used for neutron crystallography. Tutorials and examples are available in the documentation tab.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsSoftware for determination of cryo-EM structures. It employs an empirical Bayesian approach to refinement of (multiple) 3D reconstructions or 2D class averages in electron cryo-microscopy.
View all literature mentionsSoftware for macromolecular model building, model completion and validation, and protein modelling using X-ray data. Coot displays maps and models and allows model manipulations such as idealization, rigid-body fitting, ligand search, Ramachandran plots, non-crystallographic symmetry and more. Source code is available.
View all literature mentionsSoftware for macromolecular model building, model completion and validation, and protein modelling using X-ray data. Coot displays maps and models and allows model manipulations such as idealization, rigid-body fitting, ligand search, Ramachandran plots, non-crystallographic symmetry and more. Source code is available.
View all literature mentionsSoftware for determination of cryo-EM structures. It employs an empirical Bayesian approach to refinement of (multiple) 3D reconstructions or 2D class averages in electron cryo-microscopy.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsA Python-based software suite for the automated determination of molecular structures using X-ray crystallography and other methods. Phenix includes programs for assessing data quality, experimental phasing, molecular replacement, model building, structure refinement, and validation. It also includes tools for reflection data and creating maps and models. Phenix can also be used for neutron crystallography. Tutorials and examples are available in the documentation tab.
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis monoclonal targets Actin antibody [AC-40]
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
