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- EMDB-25903: Cryo-electron microscopy of Adeno-associated virus serotype 4 at 2.2 A -
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Open data
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Basic information
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Title | Cryo-electron microscopy of Adeno-associated virus serotype 4 at 2.2 A | |||||||||
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![]() | AAV4 / adeno-associated virus / serotype 4 / VIRUS LIKE PARTICLE | |||||||||
Function / homology | Phospholipase A2-like domain / Phospholipase A2-like domain / Parvovirus coat protein VP2 / Parvovirus coat protein VP1/VP2 / Parvovirus coat protein VP2 / Capsid/spike protein, ssDNA virus / T=1 icosahedral viral capsid / structural molecule activity / Capsid![]() | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.21 Å | |||||||||
![]() | Zane GM / Silveria MA | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structure of adeno-associated virus 4 at 2.2 Å resolution. Authors: Grant Zane / Mark Silveria / Nancy Meyer / Tommi White / Rui Duan / Xiaoqin Zou / Michael Chapman / ![]() Abstract: Adeno-associated virus (AAV) is the vector of choice for several approved gene-therapy treatments and is the basis for many ongoing clinical trials. Various strains of AAV exist (referred to as ...Adeno-associated virus (AAV) is the vector of choice for several approved gene-therapy treatments and is the basis for many ongoing clinical trials. Various strains of AAV exist (referred to as serotypes), each with their own transfection characteristics. Here, a high-resolution cryo-electron microscopy structure (2.2 Å) of AAV serotype 4 (AAV4) is presented. The receptor responsible for transduction of the AAV4 clade of AAV viruses (including AAV11, AAV12 and AAVrh32.33) is unknown. Other AAVs interact with the same cell receptor, adeno-associated virus receptor (AAVR), in one of two different ways. AAV5-like viruses interact exclusively with the polycystic kidney disease-like 1 (PKD1) domain of AAVR, while most other AAVs interact primarily with the PKD2 domain. A comparison of the present AAV4 structure with prior corresponding structures of AAV5, AAV2 and AAV1 in complex with AAVR provides a foundation for understanding why the AAV4-like clade is unable to interact with either PKD1 or PKD2 of AAVR. The conformation of the AAV4 capsid in variable regions I, III, IV and V on the viral surface appears to be sufficiently different from AAV2 to ablate binding with PKD2. Differences between AAV4 and AAV5 in variable region VII appear to be sufficient to exclude binding with PKD1. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 240.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.8 KB 19.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 16 KB | Display | ![]() |
Images | ![]() | 250.3 KB | ||
Filedesc metadata | ![]() | 6.8 KB | ||
Others | ![]() ![]() | 673.8 MB 673.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7thrMC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.50799 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_25903_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_25903_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : Adeno-associated virus
Entire | Name: ![]() ![]() |
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Components |
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-Supramolecule #1: Adeno-associated virus
Supramolecule | Name: Adeno-associated virus / type: virus / ID: 1 / Parent: 0 / Macromolecule list: #1 / NCBI-ID: 272636 / Sci species name: Adeno-associated virus / Sci species strain: Serotype 4 / Virus type: VIRUS-LIKE PARTICLE / Virus isolate: SEROTYPE / Virus enveloped: No / Virus empty: Yes |
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Host (natural) | Organism: ![]() |
Molecular weight | Theoretical: 3.746 MDa |
Virus shell | Shell ID: 1 / Name: Capsid / Diameter: 250.0 Å / T number (triangulation number): 1 |
-Macromolecule #1: Capsid
Macromolecule | Name: Capsid / type: protein_or_peptide / ID: 1 / Details: VP1 sequence of AAV4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 80.688023 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: TTDGYLPDWL EDNLSEGVRE WWALQPGAPK PKANQQHQDN ARGLVLPGYK YLGPGNGLDK GEPVNAADAA ALEHDKAYDQ QLKAGDNPY LKYNHADAEF QQRLQGDTSF GGNLGRAVFQ AKKRVLEPLG LVEQAGETAP GKKRPLIESP QQPDSSTGIG K KGKQPAKK ...String: TTDGYLPDWL EDNLSEGVRE WWALQPGAPK PKANQQHQDN ARGLVLPGYK YLGPGNGLDK GEPVNAADAA ALEHDKAYDQ QLKAGDNPY LKYNHADAEF QQRLQGDTSF GGNLGRAVFQ AKKRVLEPLG LVEQAGETAP GKKRPLIESP QQPDSSTGIG K KGKQPAKK KLVFEDETGA GDGPPEGSTS GAMSDDSEMR AAAGGAAVEG GQGADGVGNA SGDWHCDSTW SEGHVTTTST RT WVLPTYN NHLYKRLGES LQSNTYNGFS TPWGYFDFNR FHCHFSPRDW QRLINNNWGM RPKAMRVKIF NIQVKEVTTS NGE TTVANN LTSTVQIFAD SSYELPYVMD AGQEGSLPPF PNDVFMVPQY GYCGLVTGNT SQQQTDRNAF YCLEYFPSQM LRTG NNFEI TYSFEKVPFH SMYAHSQSLD RLMNPLIDQY LWGLQSTTTG TTLNAGTATT NFTKLRPTNF SNFKKNWLPG PSIKQ QGFS KTANQNYKIP ATGSDSLIKY ETHSTLDGRW SALTPGPPMA TAGPADSKFS NSQLIFAGPK QNGNTATVPG TLIFTS EEE LAATNATDTD MWGNLPGGDQ SNSNLPTVDR LTALGAVPGM VWQNRDIYYQ GPIWAKIPHT DGHFHPSPLI GGFGLKH PP PQIFIKNTPV PANPATTFSS TPVNSFITQY STGQVSVQID WEIQKERSKR WNPEVQFTSN YGQQNSLLWA PDAAGKYT E PRAIGTRYLT HHL UniProtKB: Capsid |
-Macromolecule #2: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 2 / Number of copies: 2 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Macromolecule #3: water
Macromolecule | Name: water / type: ligand / ID: 3 / Number of copies: 219 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.33 mg/mL | |||||||||
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Buffer | pH: 7.4 Component:
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Grid | Model: PELCO Ultrathin Carbon with Lacey Carbon / Material: COPPER / Mesh: 400 / Support film - Material: CARBON / Support film - topology: LACEY / Support film - Film thickness: 3 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 101.325 kPa | |||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 298 K / Instrument: FEI VITROBOT MARK IV / Details: blot force: 4 time: 2 s. | |||||||||
Details | The sample was isolated by multiple rounds of cesium chloride density centrifugation and dialyzed into a HEPES-buffered, sodium chloride solution (see Meyer et al., 2019 Bioprotocols paper). |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Number grids imaged: 1 / Number real images: 4809 / Average exposure time: 1.4 sec. / Average electron dose: 48.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.6 µm / Nominal magnification: 16500 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model | PDB ID: Chain - Chain ID: A / Chain - Residue range: 211-734 / Chain - Source name: PDB / Chain - Initial model type: experimental model |
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Details | Link to CNS_RSRef software: https://chapman.missouri.edu/software/ |
Output model | ![]() PDB-7thr: |