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- EMDB-20630: The atomic structure of a human adeno-associated virus capsid iso... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-20630 | ||||||||||||||||||||||||
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Title | The atomic structure of a human adeno-associated virus capsid isolate (AAVhu69/AAVv66) | ||||||||||||||||||||||||
![]() | adeno-associated virus capsid isolate (AAVhu69/AAVv66) | ||||||||||||||||||||||||
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![]() | adeno-associated virus / AAV / VIRUS | ||||||||||||||||||||||||
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 protein VP1![]() | ||||||||||||||||||||||||
Biological species | ![]() ![]() | ||||||||||||||||||||||||
Method | single particle reconstruction / Resolution: 2.46 Å | ||||||||||||||||||||||||
![]() | Hsu H-L / Brown A | ||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural characterization of a novel human adeno-associated virus capsid with neurotropic properties. Authors: Hung-Lun Hsu / Alexander Brown / Anna B Loveland / Anoushka Lotun / Meiyu Xu / Li Luo / Guangchao Xu / Jia Li / Lingzhi Ren / Qin Su / Dominic J Gessler / Yuquan Wei / Phillip W L Tai / ...Authors: Hung-Lun Hsu / Alexander Brown / Anna B Loveland / Anoushka Lotun / Meiyu Xu / Li Luo / Guangchao Xu / Jia Li / Lingzhi Ren / Qin Su / Dominic J Gessler / Yuquan Wei / Phillip W L Tai / Andrei A Korostelev / Guangping Gao / ![]() ![]() Abstract: Recombinant adeno-associated viruses (rAAVs) are currently considered the safest and most reliable gene delivery vehicles for human gene therapy. Three serotype capsids, AAV1, AAV2, and AAV9, have ...Recombinant adeno-associated viruses (rAAVs) are currently considered the safest and most reliable gene delivery vehicles for human gene therapy. Three serotype capsids, AAV1, AAV2, and AAV9, have been approved for commercial use in patients, but they may not be suitable for all therapeutic contexts. Here, we describe a novel capsid identified in a human clinical sample by high-throughput, long-read sequencing. The capsid, which we have named AAVv66, shares high sequence similarity with AAV2. We demonstrate that compared to AAV2, AAVv66 exhibits enhanced production yields, virion stability, and CNS transduction. Unique structural properties of AAVv66 visualized by cryo-EM at 2.5-Å resolution, suggest that critical residues at the three-fold protrusion and at the interface of the five-fold axis of symmetry likely contribute to the beneficial characteristics of AAVv66. Our findings underscore the potential of AAVv66 as a gene therapy vector. | ||||||||||||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 675.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13.7 KB 13.7 KB | Display Display | ![]() |
Images | ![]() | 253.6 KB | ||
Filedesc metadata | ![]() | 5.6 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 6u3qMC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | adeno-associated virus capsid isolate (AAVhu69/AAVv66) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.059 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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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: all / NCBI-ID: 272636 / Sci species name: Adeno-associated virus / Virus type: VIRION / Virus isolate: SEROTYPE / Virus enveloped: No / Virus empty: No |
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-Macromolecule #1: Capsid protein VP1
Macromolecule | Name: Capsid protein VP1 / type: protein_or_peptide / ID: 1 / Number of copies: 60 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 81.823031 KDa |
Sequence | String: MAADGYLPDW LEDTLSEGIR QWWKLKPGPP PPKPAERHQD DSRGLVLPGY KYLGPFNGLD KGEPVNEADA AALEHDKAYD RQLDSGDNP YLKYNHADAE FQERLKEDTS FGGNLGRAVF QAKKRVLEPL GLVEEPVKTA PGKKRPVEHS PAEPDSSSGT G KAGQQPAR ...String: MAADGYLPDW LEDTLSEGIR QWWKLKPGPP PPKPAERHQD DSRGLVLPGY KYLGPFNGLD KGEPVNEADA AALEHDKAYD RQLDSGDNP YLKYNHADAE FQERLKEDTS FGGNLGRAVF QAKKRVLEPL GLVEEPVKTA PGKKRPVEHS PAEPDSSSGT G KAGQQPAR KRLNFGQTGD ADSVPDPQPL GQPPAAPSGL GTNTMATGSG APMADNNEGA DGVGNSSGNW HCDSTWMGDR VI TTSTRTW ALPTYNNHLY KQISSQSGAS NDNHYFGYST PWGYFDFNRF HCHFSPRDWQ RLINNNWGFR PKRLNFKLFN IQV KEVTQN DGTTTIANNL TSTVQVFTDS EYQLPYVLGS AHQGCLPPFP ADVFMVPQYG YLTLNNGSQA VGRSSFYCLE YFPS QMLRT GNNFTFSYTF EDVPFHSSYA HSQSLDRLMN PLIDQYLYYL SKTNAPSGTT TMSRLQFSQA GASDIRDQSR NWLPG PCYR QQRVSKTAAD NNNSDYSWTG ATKYHLNGRD SLVNPGPAMA SHKDDEEKYF PQSGVLIFGK QDSGKTNVDI EKVMIT DEE EIRTTNPVAT EQYGSVSTNL QSGNTQAATT DVNTQGVLPG MVWQDRDVYL QGPIWAKIPH TDGHFHPSPL MGGFGLK HP PPQILIKNTP VPANPSTTFS AAKFASFITQ YSTGQVSVEI EWELQKENSK RWNPEIQYTS NYNKSVNVDF TVDTNGVY S EPRPIGTRYL TRNL UniProtKB: Capsid protein VP1 |
-Experimental details
-Structure determination
![]() | single particle reconstruction |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7 Component:
Details: filtered through 0.22 um filter | |||||||||||||||||||||
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Grid | Material: GOLD / Mesh: 300 / Support film - Material: CARBON / Support film - topology: LACEY / Support film - Film thickness: 3 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 48.62 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |