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- EMDB-61205: Structure of AAV8 in the complex of AAV8 with its receptor -

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Open data


ID or keywords:

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Basic information

Entry
Database: EMDB / ID: EMD-61205
TitleStructure of AAV8 in the complex of AAV8 with its receptor
Map data
Sample
  • Virus: adeno-associated virus 8
    • Protein or peptide: Capsid protein
KeywordsAAV8 / virus / complex
Function / homology
Function and homology information


T=1 icosahedral viral capsid / nucleotide binding / structural molecule activity
Similarity search - Function
Phospholipase A2-like domain / Phospholipase A2-like domain / Parvovirus coat protein VP2 / Parvovirus coat protein VP1/VP2 / Parvovirus coat protein VP1/VP2 / Capsid/spike protein, ssDNA virus
Similarity search - Domain/homology
Biological speciesAdeno-associated virus - 8 / adeno-associated virus 8
Methodsingle particle reconstruction / cryo EM / Resolution: 2.32 Å
AuthorsXu H / Wang GP / Su XD
Funding support China, 1 items
OrganizationGrant numberCountry
Ministry of Science and Technology (MoST, China)2021YFC2301402 China
CitationJournal: Cell / Year: 2025
Title: An alternate receptor for adeno-associated viruses.
Authors: Bijay P Dhungel / Hua Xu / Rajini Nagarajah / Joseph Vitale / Alex C H Wong / Divya Gokal / Yue Feng / Mehdi Sharifi Tabar / Cynthia Metierre / Chirag Parsania / Xiaohui Song / Guopeng Wang ...Authors: Bijay P Dhungel / Hua Xu / Rajini Nagarajah / Joseph Vitale / Alex C H Wong / Divya Gokal / Yue Feng / Mehdi Sharifi Tabar / Cynthia Metierre / Chirag Parsania / Xiaohui Song / Guopeng Wang / Xiao-Dong Su / Charles G Bailey / John E J Rasko /
Abstract: Systemic gene therapy using adeno-associated virus (AAV) vectors is approved for the treatment of several genetic disorders, but challenges and toxicities associated with high vector doses remain. We ...Systemic gene therapy using adeno-associated virus (AAV) vectors is approved for the treatment of several genetic disorders, but challenges and toxicities associated with high vector doses remain. We report an alternate receptor for AAV (AAVR2, carboxypeptidase D [CPD]), which is distinct from the multi-serotype AAV receptor (AAVR). AAVR2 enables the transduction of clade E AAVs, including AAV8, and determines an exclusive AAVR-independent transduction pathway for AAV11 and AAV12. We characterized direct binding between the AAV8 capsid and AAVR2 by cryo-electron microscopy (cryo-EM) and identified contact residues. We observed that AAV8 directly binds to the carboxypeptidase-like domain 1 of AAVR2 via its variable region VIII and demonstrated that AAV capsids that lack AAVR2 binding can be bioengineered to engage with AAVR2. Finally, we overexpressed a minimal functional AAVR2 to enhance AAV transduction in vivo. Our study provides insights into AAV biology and clinically deployable solutions to reduce dose-related toxicities associated with AAV vectors.
History
DepositionAug 19, 2024-
Header (metadata) releaseJul 23, 2025-
Map releaseJul 23, 2025-
UpdateSep 24, 2025-
Current statusSep 24, 2025Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_61205.map.gz / Format: CCP4 / Size: 371.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.07 Å/pix.
x 460 pix.
= 492.2 Å
1.07 Å/pix.
x 460 pix.
= 492.2 Å
1.07 Å/pix.
x 460 pix.
= 492.2 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.07 Å
Density
Contour LevelBy AUTHOR: 0.04
Minimum - Maximum-0.13883547 - 0.26634085
Average (Standard dev.)0.00075661816 (±0.010859941)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions460460460
Spacing460460460
CellA=B=C: 492.2 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_61205_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #2

Fileemd_61205_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : adeno-associated virus 8

EntireName: adeno-associated virus 8
Components
  • Virus: adeno-associated virus 8
    • Protein or peptide: Capsid protein

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Supramolecule #1: adeno-associated virus 8

SupramoleculeName: adeno-associated virus 8 / type: virus / ID: 1 / Parent: 0 / Macromolecule list: all / NCBI-ID: 202813 / Sci species name: adeno-associated virus 8 / Virus type: VIRION / Virus isolate: SEROTYPE / Virus enveloped: No / Virus empty: Yes

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Macromolecule #1: Capsid protein

MacromoleculeName: Capsid protein / type: protein_or_peptide / ID: 1 / Number of copies: 60 / Enantiomer: LEVO
Source (natural)Organism: Adeno-associated virus - 8
Molecular weightTheoretical: 81.833047 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MAADGYLPDW LEDNLSEGIR EWWALKPGAP KPKANQQKQD DGRGLVLPGY KYLGPFNGLD KGEPVNAADA AALEHDKAYD QQLQAGDNP YLRYNHADAE FQERLQEDTS FGGNLGRAVF QAKKRVLEPL GLVEEGAKTA PGKKRPVEPS PQRSPDSSTG I GKKGQQPA ...String:
MAADGYLPDW LEDNLSEGIR EWWALKPGAP KPKANQQKQD DGRGLVLPGY KYLGPFNGLD KGEPVNAADA AALEHDKAYD QQLQAGDNP YLRYNHADAE FQERLQEDTS FGGNLGRAVF QAKKRVLEPL GLVEEGAKTA PGKKRPVEPS PQRSPDSSTG I GKKGQQPA RKRLNFGQTG DSESVPDPQP LGEPPAAPSG VGPNTMAAGG GAPMADNNEG ADGVGSSSGN WHCDSTWLGD RV ITTSTRT WALPTYNNHL YKQISNGTSG GATNDNTYFG YSTPWGYFDF NRFHCHFSPR DWQRLINNNW GFRPKRLSFK LFN IQVKEV TQNEGTKTIA NNLTSTIQVF TDSEYQLPYV LGSAHQGCLP PFPADVFMIP QYGYLTLNNG SQAVGRSSFY CLEY FPSQM LRTGNNFQFT YTFEDVPFHS SYAHSQSLDR LMNPLIDQYL YYLSRTQTTG GTANTQTLGF SQGGPNTMAN QAKNW LPGP CYRQQRVSTT TGQNNNSNFA WTAGTKYHLN GRNSLANPGI AMATHKDDEE RFFPSNGILI FGKQNAARDN ADYSDV MLT SEEEIKTTNP VATEEYGIVA DNLQQQNTAP QIGTVNSQGA LPGMVWQNRD VYLQGPIWAK IPHTDGNFHP SPLMGGF GL KHPPPQILIK NTPVPADPPT TFNQSKLNSF ITQYSTGQVS VEIEWELQKE NSKRWNPEIQ YTSNYYKSTS VDFAVNTE G VYSEPRPIGT RYLTRNL

UniProtKB: Capsid protein

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration0.8 mg/mL
BufferpH: 7.2
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.32 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 235305
Initial angle assignmentType: PROJECTION MATCHING
Final angle assignmentType: PROJECTION MATCHING

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