|Entry||Database: EMDB / ID: 5890|
|Title||Cryo-EM structure of MAVS CARD filament|
|Map data||Cryo-EM map of MAVS CARD filament|
|Sample||MAVS CARD filament|
|Keywords||Innate immunity / helical filament|
|Function / homology||Ovarian tumor domain proteases / NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 / TRAF3-dependent IRF activation pathway / Mitochondrial antiviral-signalling protein / Caspase recruitment domain / TRAF6 mediated NF-kB activation / TRAF6 mediated IRF7 activation / Negative regulators of DDX58/IFIH1 signaling / DDX58/IFIH1-mediated induction of interferon-alpha/beta / Caspase recruitment domain ...Ovarian tumor domain proteases / NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 / TRAF3-dependent IRF activation pathway / Mitochondrial antiviral-signalling protein / Caspase recruitment domain / TRAF6 mediated NF-kB activation / TRAF6 mediated IRF7 activation / Negative regulators of DDX58/IFIH1 signaling / DDX58/IFIH1-mediated induction of interferon-alpha/beta / Caspase recruitment domain / positive regulation of IP-10 production / regulation of peroxisome organization / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of response to cytokine stimulus / positive regulation of interferon-beta secretion / CARD domain binding / positive regulation of tumor necrosis factor secretion / positive regulation of type I interferon-mediated signaling pathway / positive regulation of interferon-alpha secretion / cellular response to exogenous dsRNA / peroxisomal membrane / positive regulation of interferon-alpha production / positive regulation of interferon-beta production / activation of innate immune response / positive regulation of defense response to virus by host / positive regulation of interleukin-6 secretion / go:0042993: / mitochondrial membrane / positive regulation of interleukin-8 production / negative regulation of viral genome replication / positive regulation of protein import into nucleus, translocation / positive regulation of tumor necrosis factor production / negative regulation of type I interferon production / defense response to virus / go:0004871: / positive regulation of DNA binding transcription factor activity / mitochondrial outer membrane / positive regulation of I-kappaB kinase/NF-kappaB signaling / protein deubiquitination / positive regulation of protein phosphorylation / defense response to bacterium / viral process / protein kinase binding / innate immune response / signal transduction / positive regulation of transcription by RNA polymerase II / mitochondrion / integral component of membrane / Mitochondrial antiviral-signaling protein|
Function and homology information
|Source||Homo sapiens (human)|
|Method||helical reconstruction / cryo EM / 9.6 Å resolution|
|Authors||Xu H / He X / Zheng H / Huang LJ / Hou F / Yu Z / de la Cruz MJ / Borkowski B / Zhang X / Chen ZJ / Jiang Q-X|
|Citation||Journal: Elife / Year: 2014|
Title: Structural basis for the prion-like MAVS filaments in antiviral innate immunity.
Authors: Hui Xu / Xiaojing He / Hui Zheng / Lily J Huang / Fajian Hou / Zhiheng Yu / Michael Jason de la Cruz / Brian Borkowski / Xuewu Zhang / Zhijian J Chen / Qiu-Xing Jiang
Abstract: Mitochondrial antiviral signaling (MAVS) protein is required for innate immune responses against RNA viruses. In virus-infected cells MAVS forms prion-like aggregates to activate antiviral signaling ...Mitochondrial antiviral signaling (MAVS) protein is required for innate immune responses against RNA viruses. In virus-infected cells MAVS forms prion-like aggregates to activate antiviral signaling cascades, but the underlying structural mechanism is unknown. Here we report cryo-electron microscopic structures of the helical filaments formed by both the N-terminal caspase activation and recruitment domain (CARD) of MAVS and a truncated MAVS lacking part of the proline-rich region and the C-terminal transmembrane domain. Both structures are left-handed three-stranded helical filaments, revealing specific interfaces between individual CARD subunits that are dictated by electrostatic interactions between neighboring strands and hydrophobic interactions within each strand. Point mutations at multiple locations of these two interfaces impaired filament formation and antiviral signaling. Super-resolution imaging of virus-infected cells revealed rod-shaped MAVS clusters on mitochondria. These results elucidate the structural mechanism of MAVS polymerization, and explain how an α-helical domain uses distinct chemical interactions to form self-perpetuating filaments. DOI: http://dx.doi.org/10.7554/eLife.01489.001.
|Validation Report||PDB-ID: 3j6c|
SummaryFull reportAbout validation report
|Date||Deposition: Jan 22, 2014 / Header (metadata) release: Feb 19, 2014 / Map release: Mar 5, 2014 / Last update: Oct 7, 2015|
|Structure viewer||EM map: |
Downloads & links
|File||emd_5890.map.gz (map file in CCP4 format, 978 KB)|
|Projections & slices|
Images are generated by Spider.
|Voxel size||X=Y=Z: 2.333 Å|
CCP4 map header:
-Entire MAVS CARD filament
|Entire||Name: MAVS CARD filament / Number of components: 1 / Oligomeric State: polymer|
|Mass||Theoretical: 546 kDa|
-Component #1: protein, Mitochondrial antiviral-signaling protein (MAVS)
|Protein||Name: Mitochondrial antiviral-signaling protein (MAVS) / a.k.a: IPS1, KIAA1271, VISA / Oligomeric Details: polymer / Recombinant expression: Yes|
|Mass||Theoretical: 13 kDa|
|Source||Species: Homo sapiens (human)|
|Source (engineered)||Expression System: Homo sapiens (human) / Vector: pcDNA3 / Cell of expression system: HEK293T|
|External references||UniProt: UniProt:Q7Z434|
|Specimen||Specimen state: filament / Method: cryo EM|
|Helical parameters||Axial symmetry: C3 (3 fold cyclic) / Hand: LEFT HANDED / Delta z: 16.8 Å / Delta phi: 53.6 deg.|
|Sample solution||Buffer solution: 20mM Tris-HCl, 50mM NaCl, 1mM DTT / pH: 7.5|
|Support film||Quantifoil grids coated with thin carbon on top|
|Vitrification||Instrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 100 %|
-Electron microscopy imaging
|Imaging||Microscope: JEOL 2200FS / Date: Oct 20, 2011|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Electron dose: 20 e/Å2 / Illumination mode: FLOOD BEAM|
|Lens||Magnification: 60000 X (nominal), 61950 X (calibrated)|
Astigmatism: Objective lens astigmatism was corrected at 100,000x magnification
Cs: 2 mm / Imaging mode: BRIGHT FIELD / Defocus: 800 - 2000 nm / Energy filter: JEOL omega filter / Energy window: 0-35 eV
|Specimen Holder||Model: GATAN LIQUID NITROGEN|
|Camera||Detector: KODAK SO-163 FILM|
|Image acquisition||Scanner: ZEISS SCAI / Sampling size: 7 microns / URL of raw data: http://dx.doi.org/10.6019/EMPIAR-10014|
|Raw data||EMPIAR-10014 (Title: MAVS CARD and DeltaProTM filaments / Data size: 35.3 GB / Data #1: CARD set1 micrographs [micrographs - single frame] / Data #2: CARD set2 micrographs [micrographs - single frame] / Data #3: CARD set3 micrographs [micrographs - single frame] / Data #4: CARD set4 micrographs [micrographs - single frame]|
Data #5: CARD set1 segments [picked particles - single frame - unprocessed]
Data #6: CARD set2 segments [picked particles - single frame - unprocessed]
Data #7: CARD set3 segments [picked particles - single frame - unprocessed]
Data #8: CARD set4 segments [picked particles - single frame - unprocessed]
Data #9: DeltProTM micrographs [micrographs - single frame]
Data #10: DeltaProTM segments [picked particles - single frame - unprocessed])
|Processing||Method: helical reconstruction / Details: IHRSR|
|3D reconstruction||Algorithm: IHRSR / Software: Spider, MRC, EMAN, IMAGIC4D / CTF correction: Each filament segment|
Details: Final data were calculated from three separate datasets from three sessions of data collection. The handedness of the map was determined by cryo-electron tomography.
Resolution: 9.6 Å / Resolution method: FSC 0.5, gold-standard
-Atomic model buiding
|Modeling #1||Software: Chimera, SITUS / Refinement protocol: rigid body / Refinement space: REAL|
Details: The docking of one X-ray model into a segmented map corresponding to one subunit was first done manually in Chimera, and then optimized using SITUS.
Input PDB model: 2VGQ
Chain ID: A
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