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- EMDB-9672: Adeno-Associated Virus 2 in complex with AAVR -

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Basic information

Entry
Database: EMDB / ID: EMD-9672
TitleAdeno-Associated Virus 2 in complex with AAVR
Map data
Sample
  • Complex: AAV2 in complex with AAVRAdeno-associated virus
    • Complex: Adeno-associated virus 2
      • Protein or peptide: Capsid protein VP1
    • Complex: AAVR PKD2
      • Protein or peptide: Dyslexia-associated protein KIAA0319-like protein
KeywordsAAV2 / VIRUS
Function / homology
Function and homology information


permeabilization of host organelle membrane involved in viral entry into host cell / symbiont entry into host cell via permeabilization of inner membrane / host cell nucleolus / T=1 icosahedral viral capsid / neuron migration / cytoplasmic vesicle / clathrin-dependent endocytosis of virus by host cell / Golgi membrane / structural molecule activity / virion attachment to host cell ...permeabilization of host organelle membrane involved in viral entry into host cell / symbiont entry into host cell via permeabilization of inner membrane / host cell nucleolus / T=1 icosahedral viral capsid / neuron migration / cytoplasmic vesicle / clathrin-dependent endocytosis of virus by host cell / Golgi membrane / structural molecule activity / virion attachment to host cell / nucleolus / Golgi apparatus / membrane / plasma membrane
Similarity search - Function
Dyslexia-associated protein KIAA0319-like / MANSC domain / MANSC domain profile. / PKD domain / Polycystic kidney disease (PKD) domain profile. / PKD domain / PKD domain superfamily / PKD/Chitinase domain / Repeats in polycystic kidney disease 1 (PKD1) and other proteins / Phospholipase A2-like domain ...Dyslexia-associated protein KIAA0319-like / MANSC domain / MANSC domain profile. / PKD domain / Polycystic kidney disease (PKD) domain profile. / PKD domain / PKD domain superfamily / PKD/Chitinase domain / Repeats in polycystic kidney disease 1 (PKD1) and other proteins / 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 / Immunoglobulin-like fold
Similarity search - Domain/homology
Capsid protein VP1 / Dyslexia-associated protein KIAA0319-like protein
Similarity search - Component
Biological speciesAdeno-associated virus 2 (isolate Srivastava/1982) / Homo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.84 Å
AuthorsLou ZY / Zhang R
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China21572116 China
CitationJournal: Nat Microbiol / Year: 2019
Title: Adeno-associated virus 2 bound to its cellular receptor AAVR.
Authors: Ran Zhang / Lin Cao / Mengtian Cui / Zixian Sun / Mingxu Hu / Rouxuan Zhang / William Stuart / Xiaochu Zhao / Zirui Yang / Xueming Li / Yuna Sun / Shentao Li / Wei Ding / Zhiyong Lou / Zihe Rao /
Abstract: Adeno-associated virus (AAV) is a leading vector for virus-based gene therapy. The receptor for AAV (AAVR; also named KIAA0319L) was recently identified, and the precise characterization of AAV-AAVR ...Adeno-associated virus (AAV) is a leading vector for virus-based gene therapy. The receptor for AAV (AAVR; also named KIAA0319L) was recently identified, and the precise characterization of AAV-AAVR recognition is in immediate demand. Taking advantage of a particle-filtering algorithm, we report here the cryo-electron microscopy structure of the AAV2-AAVR complex at 2.8 Å resolution. This structure reveals that of the five Ig-like polycystic kidney disease (PKD) domains in AAVR, PKD2 binds directly to the spike region of the AAV2 capsid adjacent to the icosahedral three-fold axis. Residues in strands B and E, and the BC loop of AAVR PKD2 interact directly with the AAV2 capsid. The interacting residues in the AAV2 capsid are mainly in AAV-featured variable regions. Mutagenesis of the amino acids at the AAV2-AAVR interface reduces binding activity and viral infectivity. Our findings provide insights into the biology of AAV entry with high-resolution details, providing opportunities for the development of new AAV vectors for gene therapy.
History
DepositionSep 29, 2018-
Header (metadata) releaseMar 20, 2019-
Map releaseMar 20, 2019-
UpdateMar 27, 2024-
Current statusMar 27, 2024Processing site: PDBj / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.0025
  • Imaged by UCSF Chimera
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  • Surface view colored by radius
  • Surface level: 0.0025
  • Imaged by UCSF Chimera
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  • Surface view with fitted model
  • Atomic models: PDB-6ihb
  • Surface level: 0.015
  • Imaged by UCSF Chimera
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  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6ihb
  • Imaged by Jmol
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

Downloads & links

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Map

FileDownload / File: emd_9672.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Voxel sizeX=Y=Z: 0.93 Å
Density
Contour LevelBy AUTHOR: 0.0025 / Movie #1: 0.0025
Minimum - Maximum-0.14267884 - 0.14006905
Average (Standard dev.)0.0010085038 (±0.00828199)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin-220-220-220
Dimensions440440440
Spacing440440440
CellA=B=C: 409.2 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z0.930.930.93
M x/y/z440440440
origin x/y/z0.0000.0000.000
length x/y/z409.200409.200409.200
α/β/γ90.00090.00090.000
MAP C/R/S123
start NC/NR/NS-220-220-220
NC/NR/NS440440440
D min/max/mean-0.1430.1400.001

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Supplemental data

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Sample components

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Entire : AAV2 in complex with AAVR

EntireName: AAV2 in complex with AAVRAdeno-associated virus
Components
  • Complex: AAV2 in complex with AAVRAdeno-associated virus
    • Complex: Adeno-associated virus 2
      • Protein or peptide: Capsid protein VP1
    • Complex: AAVR PKD2
      • Protein or peptide: Dyslexia-associated protein KIAA0319-like protein

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Supramolecule #1: AAV2 in complex with AAVR

SupramoleculeName: AAV2 in complex with AAVR / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all

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Supramolecule #2: Adeno-associated virus 2

SupramoleculeName: Adeno-associated virus 2 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #2
Source (natural)Organism: Adeno-associated virus 2 (isolate Srivastava/1982)

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Supramolecule #3: AAVR PKD2

SupramoleculeName: AAVR PKD2 / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Dyslexia-associated protein KIAA0319-like protein

MacromoleculeName: Dyslexia-associated protein KIAA0319-like protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 10.31445 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString:
KNRPPIAIVS PQFQEISLPT TSTVIDGSQS TDDDKIVQYH WEELKGPLRE EKISEDTAIL KLSKLVPGNY TFSLTVVDSD GATNSTTAN LTVNK

UniProtKB: Dyslexia-associated protein KIAA0319-like protein

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Macromolecule #2: Capsid protein VP1

MacromoleculeName: Capsid protein VP1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Adeno-associated virus 2 (isolate Srivastava/1982)
Molecular weightTheoretical: 82.031352 KDa
SequenceString: MAADGYLPDW LEDTLSEGIR QWWKLKPGPP PPKPAERHKD DSRGLVLPGY KYLGPFNGLD KGEPVNEADA AALEHDKAYD RQLDSGDNP YLKYNHADAE FQERLKEDTS FGGNLGRAVF QAKKRVLEPL GLVEEPVKTA PGKKRPVEHS PVEPDSSSGT G KAGQQPAR ...String:
MAADGYLPDW LEDTLSEGIR QWWKLKPGPP PPKPAERHKD DSRGLVLPGY KYLGPFNGLD KGEPVNEADA AALEHDKAYD RQLDSGDNP YLKYNHADAE FQERLKEDTS FGGNLGRAVF QAKKRVLEPL GLVEEPVKTA PGKKRPVEHS PVEPDSSSGT 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 SRTNTPSGTT TQSRLQFSQA GASDIRDQSR NWLPG PCYR QQRVSKTSAD NNNSEYSWTG ATKYHLNGRD SLVNPGPAMA SHKDDEEKFF PQSGVLIFGK QGSEKTNVDI EKVMIT DEE EIRTTNPVAT EQYGSVSTNL QRGNRQAATA DVNTQGVLPG MVWQDRDVYL QGPIWAKIPH TDGHFHPSPL MGGFGLK HP PPQILIKNTP VPANPSTTFS AAKFASFITQ YSTGQVSVEI EWELQKENSK RWNPEIQYTS NYNKSVNVDF TVDTNGVY S EPRPIGTRYL TRNL

UniProtKB: Capsid protein VP1

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation state2D array

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Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TECNAI ARCTICA
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy
Image recordingFilm or detector model: FEI FALCON II (4k x 4k) / Average electron dose: 1.53 e/Å2
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.84 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 16820

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