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- PDB-3j6c: Cryo-EM structure of MAVS CARD filament -

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Entry
Database: PDB / ID: 3j6c
TitleCryo-EM structure of MAVS CARD filament
ComponentsMitochondrial antiviral-signaling protein
KeywordsSIGNALING PROTEIN / Innate immunity / helical filament
Function / homology
Function and homology information


positive regulation of IP-10 production / regulation of peroxisome organization / RIG-I binding / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of myeloid dendritic cell cytokine production / CARD domain binding / NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 / positive regulation of response to cytokine stimulus / protein localization to mitochondrion / positive regulation of type I interferon-mediated signaling pathway ...positive regulation of IP-10 production / regulation of peroxisome organization / RIG-I binding / positive regulation of chemokine (C-C motif) ligand 5 production / positive regulation of myeloid dendritic cell cytokine production / CARD domain binding / NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10 / positive regulation of response to cytokine stimulus / protein localization to mitochondrion / positive regulation of type I interferon-mediated signaling pathway / peroxisomal membrane / TRAF6 mediated IRF7 activation / negative regulation of type I interferon-mediated signaling pathway / positive regulation of NLRP3 inflammasome complex assembly / negative regulation of viral genome replication / cellular response to exogenous dsRNA / type I interferon-mediated signaling pathway / cytoplasmic pattern recognition receptor signaling pathway / positive regulation of interferon-alpha production / antiviral innate immune response / TRAF6 mediated NF-kB activation / positive regulation of type I interferon production / ubiquitin ligase complex / signaling adaptor activity / positive regulation of defense response to virus by host / molecular condensate scaffold activity / positive regulation of interferon-beta production / activation of innate immune response / Negative regulators of DDX58/IFIH1 signaling / positive regulation of interleukin-8 production / mitochondrial membrane / DDX58/IFIH1-mediated induction of interferon-alpha/beta / PKR-mediated signaling / positive regulation of interleukin-6 production / positive regulation of protein import into nucleus / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of DNA-binding transcription factor activity / Ovarian tumor domain proteases / positive regulation of tumor necrosis factor production / TRAF3-dependent IRF activation pathway / defense response to virus / positive regulation of canonical NF-kappaB signal transduction / mitochondrial outer membrane / molecular adaptor activity / defense response to bacterium / positive regulation of protein phosphorylation / innate immune response / protein kinase binding / SARS-CoV-2 activates/modulates innate and adaptive immune responses / signal transduction / positive regulation of transcription by RNA polymerase II / mitochondrion / identical protein binding
Similarity search - Function
IPS1, CARD domain / Caspase recruitment domain / Caspase recruitment domain / Death-like domain superfamily
Similarity search - Domain/homology
Mitochondrial antiviral-signaling protein
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 9.6 Å
AuthorsXu, H. / He, X. / Zheng, H. / Huang, L.J. / Hou, F. / Yu, Z. / de la Cruz, M.J. / Borkowski, B. / Zhang, X. / Chen, Z.J. / 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.
#1: Journal: BMC Struct Biol / Year: 2008
Title: Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain.
Authors: Jane A Potter / Richard E Randall / Garry L Taylor /
Abstract: BACKGROUND: IPS-1/MAVS/VISA/Cardif is an adaptor protein that plays a crucial role in the induction of interferons in response to viral infection. In the initial stage of the intracellular antiviral ...BACKGROUND: IPS-1/MAVS/VISA/Cardif is an adaptor protein that plays a crucial role in the induction of interferons in response to viral infection. In the initial stage of the intracellular antiviral response two RNA helicases, retinoic acid inducible gene-I (RIG-I) and melanoma differentiation-association gene 5 (MDA5), are independently able to bind viral RNA in the cytoplasm. The 62 kDa protein IPS-1/MAVS/VISA/Cardif contains an N-terminal caspase activation and recruitment (CARD) domain that associates with the CARD regions of RIG-I and MDA5, ultimately leading to the induction of type I interferons. As a first step towards understanding the molecular basis of this important adaptor protein we have undertaken structural studies of the IPS-1 MAVS/VISA/Cardif CARD region.
RESULTS: The crystal structure of human IPS-1/MAVS/VISA/Cardif CARD has been determined to 2.1A resolution. The protein was expressed and crystallized as a maltose-binding protein (MBP) fusion ...RESULTS: The crystal structure of human IPS-1/MAVS/VISA/Cardif CARD has been determined to 2.1A resolution. The protein was expressed and crystallized as a maltose-binding protein (MBP) fusion protein. The MBP and IPS-1 components each form a distinct domain within the structure. IPS-1/MAVS/VISA/Cardif CARD adopts a characteristic six-helix bundle with a Greek-key topology and, in common with a number of other known CARD structures, contains two major polar surfaces on opposite sides of the molecule. One face has a surface-exposed, disordered tryptophan residue that may explain the poor solubility of untagged expression constructs.
CONCLUSION: The IPS-1/MAVS/VISA/Cardif CARD domain adopts the classic CARD fold with an asymmetric surface charge distribution that is typical of CARD domains involved in homotypic protein-protein ...CONCLUSION: The IPS-1/MAVS/VISA/Cardif CARD domain adopts the classic CARD fold with an asymmetric surface charge distribution that is typical of CARD domains involved in homotypic protein-protein interactions. The location of the two polar areas on IPS-1/MAVS/VISA/Cardif CARD suggest possible types of associations that this domain makes with the two CARD domains of MDA5 or RIG-I. The N-terminal CARD domains of RIG-I and MDA5 share greatest sequence similarity with IPS-1/MAVS/VISA/Cardif CARD and this has allowed modelling of their structures. These models show a very different charge profile for the equivalent surfaces compared to IPS-1/MAVS/VISA/Cardif CARD.
History
DepositionFeb 4, 2014Deposition site: RCSB / Processing site: RCSB
Revision 1.0Mar 5, 2014Provider: repository / Type: Initial release
Revision 1.1Jul 18, 2018Group: Author supporting evidence / Data collection
Category: em_image_scans / em_single_particle_entity / em_software
Item: _em_software.image_processing_id
Revision 1.2Feb 21, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / em_3d_fitting_list / pdbx_initial_refinement_model / pdbx_struct_oper_list / struct_ref_seq_dif
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _em_3d_fitting_list.accession_code / _em_3d_fitting_list.initial_refinement_model_id / _em_3d_fitting_list.source_name / _em_3d_fitting_list.type / _pdbx_struct_oper_list.name / _pdbx_struct_oper_list.symmetry_operation / _pdbx_struct_oper_list.type / _struct_ref_seq_dif.details

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Structure visualization

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Assembly

Deposited unit
A: Mitochondrial antiviral-signaling protein


Theoretical massNumber of molelcules
Total (without water)10,8261
Polymers10,8261
Non-polymers00
Water0
1
A: Mitochondrial antiviral-signaling protein
x 24


Theoretical massNumber of molelcules
Total (without water)259,83224
Polymers259,83224
Non-polymers00
Water0
TypeNameSymmetry operationNumber
helical symmetry operation23
identity operation1_555x,y,z1
2


  • Idetical with deposited unit
  • helical asymmetric unit
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3


  • Idetical with deposited unit
  • helical asymmetric unit, std helical frame
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
SymmetryHelical symmetry: (Circular symmetry: 3 / Dyad axis: no / N subunits divisor: 1 / Num. of operations: 24 / Rise per n subunits: 16.8 Å / Rotation per n subunits: -53.6 °)

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Components

#1: Protein Mitochondrial antiviral-signaling protein / MAVS / CARD adapter inducing interferon beta / Cardif / Interferon beta promoter stimulator protein ...MAVS / CARD adapter inducing interferon beta / Cardif / Interferon beta promoter stimulator protein 1 / IPS-1 / Putative NF-kappa-B-activating protein 031N / Virus-induced-signaling adapter / VISA


Mass: 10826.325 Da / Num. of mol.: 1
Fragment: caspase activation recruitment domain (UNP residues 3-93)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MAVS, IPS1, KIAA1271, VISA / Plasmid: pcDNA3 / Cell line (production host): HEK293T / Production host: Homo sapiens (human) / References: UniProt: Q7Z434

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: FILAMENT / 3D reconstruction method: helical reconstruction

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Sample preparation

ComponentName: MAVS CARD filament / Type: COMPLEX / Details: polymer
Molecular weightValue: 0.546 MDa / Experimental value: NO
Buffer solutionName: 20 mM Tris-HCl, 50 mM NaCl, 1 mM DTT / pH: 7.5 / Details: 20 mM Tris-HCl, 50 mM NaCl, 1 mM DTT
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportDetails: Quantifoil grids coated with thin carbon on top
VitrificationInstrument: FEI VITROBOT MARK III / Cryogen name: ETHANE / Humidity: 100 % / Details: Plunged into liquid ethane (FEI VITROBOT MARK III)

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Electron microscopy imaging

MicroscopyModel: JEOL 2200FS / Date: Oct 20, 2011
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 60000 X / Calibrated magnification: 61950 X / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm / Cs: 2 mm
Astigmatism: Objective lens astigmatism was corrected at 100,000x magnification
Camera length: 0 mm
Specimen holderSpecimen holder model: GATAN LIQUID NITROGEN / Tilt angle max: 0 ° / Tilt angle min: 0 °
Image recordingElectron dose: 20 e/Å2 / Film or detector model: KODAK SO-163 FILM
EM imaging opticsEnergyfilter name: FEI / Energyfilter upper: 35 eV / Energyfilter lower: 0 eV
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthRelative weight: 1

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Processing

EM software
IDNameVersionCategory
1Situsmodel fitting
2UCSF Chimeramodel fitting
3EMAN3D reconstruction
4IMAGIC4D3D reconstruction
5MRC3D reconstruction
6SPIDER3D reconstruction
CTF correctionDetails: Each filament segment
Helical symmertyAngular rotation/subunit: 53.6 ° / Axial rise/subunit: 16.8 Å / Axial symmetry: C3
3D reconstructionMethod: IHRSR / Resolution: 9.6 Å / Resolution method: FSC 0.5 CUT-OFF / Nominal pixel size: 2.333 Å / Actual pixel size: 2.333 Å
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 (Helical Details: IHRSR).
Symmetry type: HELICAL
Atomic model buildingProtocol: RIGID BODY FIT / Space: REAL
Details: REFINEMENT PROTOCOL--rigid body 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.
Atomic model buildingPDB-ID: 2VGQ

2vgq


Pdb chain-ID: A / Accession code: 2VGQ / Source name: PDB / Type: experimental model
Refinement stepCycle: LAST
ProteinNucleic acidLigandSolventTotal
Num. atoms760 0 0 0 760

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