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- PDB-7wjx: Adeno-associated virus serotype 9 in complex with AAVR -

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Basic information

Entry
Database: PDB / ID: 7wjx
TitleAdeno-associated virus serotype 9 in complex with AAVR
Components
  • Capsid protein VP1
  • Dyslexia-associated protein KIAA0319-like protein
KeywordsVIRUS
Function / homology
Function and homology information


T=1 icosahedral viral capsid / neuron migration / cytoplasmic vesicle / Golgi membrane / nucleolus / structural molecule activity / 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 speciesHomo sapiens (human)
Adeno-associated virus 9
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.23 Å
AuthorsXu, G. / Lou, Z.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Mol Ther Methods Clin Dev / Year: 2022
Title: Structural basis for the neurotropic AAV9 and the engineered AAVPHP.eB recognition with cellular receptors.
Authors: Guangxue Xu / Ran Zhang / Huapeng Li / Kaixin Yin / Xinyi Ma / Zhiyong Lou /
Abstract: Clade F adeno-associated virus (AAV) 9 has been utilized as therapeutic gene delivery vector, and it is capable of crossing blood brain barrier (BBB). Recently, an AAV9-based engineering serotype ...Clade F adeno-associated virus (AAV) 9 has been utilized as therapeutic gene delivery vector, and it is capable of crossing blood brain barrier (BBB). Recently, an AAV9-based engineering serotype AAVPHP.eB with enhanced BBB crossing ability further expanded clade F AAVs' usages in the murine central nervous system (CNS) gene delivery. In this study, we determined the cryo-electron microscopy (cryo-EM) structures of the AAVPHP.eB and its parental serotype AAV9 in native form or in complex with their essential receptor AAV receptor (AAVR). These structures reveal the molecular details of their AAVR recognition, where the polycystic kidney disease repeat domain 2 (PKD2) of AAVR interacts with AAV9 and AAVPHP.eB virions at the 3-fold protrusions and the raised capsid regions between the 2- and 5-fold axes, termed the 2/5-fold wall. The interacting patterns of AAVR to AAV9 and AAVPHP.eB are similar to what was observed in AAV1/AAV2-AAVR complexes. Moreover, we found that the AAVPHP.eB variable region VIII (VR-VIII) may independently facilitate the new receptor recognition responsible for enhanced CNS transduction. Our study provides insights into the recognition principles of multiple receptors for engineered AAVPHP.eB and parental serotype AAV9, and further reveal the potential molecular basis underlying their different tropisms.
History
DepositionJan 8, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jun 15, 2022Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2022Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
R: Dyslexia-associated protein KIAA0319-like protein
A: Capsid protein VP1


Theoretical massNumber of molelcules
Total (without water)68,9462
Polymers68,9462
Non-polymers00
Water0
1
R: Dyslexia-associated protein KIAA0319-like protein
A: Capsid protein VP1
x 60


Theoretical massNumber of molelcules
Total (without water)4,136,763120
Polymers4,136,763120
Non-polymers00
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
point symmetry operation59
2


  • Idetical with deposited unit
  • icosahedral asymmetric unit
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
3
R: Dyslexia-associated protein KIAA0319-like protein
A: Capsid protein VP1
x 5


  • icosahedral pentamer
  • 345 kDa, 10 polymers
Theoretical massNumber of molelcules
Total (without water)344,73010
Polymers344,73010
Non-polymers00
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
point symmetry operation4
4
R: Dyslexia-associated protein KIAA0319-like protein
A: Capsid protein VP1
x 6


  • icosahedral 23 hexamer
  • 414 kDa, 12 polymers
Theoretical massNumber of molelcules
Total (without water)413,67612
Polymers413,67612
Non-polymers00
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
point symmetry operation5
5


  • Idetical with deposited unit
  • icosahedral asymmetric unit, std point frame
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
SymmetryPoint symmetry: (Schoenflies symbol: I (icosahedral))

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Components

#1: Protein Dyslexia-associated protein KIAA0319-like protein / Adeno-associated virus receptor / AAVR


Mass: 10471.644 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli) / References: UniProt: Q8IZA0
#2: Protein Capsid protein VP1 /


Mass: 58474.414 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Adeno-associated virus 9 / Gene: cap / Production host: Homo sapiens (human) / References: UniProt: Q6JC40

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

Component
IDNameTypeEntity IDParent-IDSource
1Adeno-associated virus 9COMPLEXall0RECOMBINANT
2AAVRCOMPLEX#11RECOMBINANT
3virusVIRUS#21RECOMBINANT
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
22Adeno-associated virus 9235455
33Homo sapiens (human)9606
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-IDCell
22Escherichia coli (E. coli)562
33Homo sapiens (human)9606HEK293
Details of virusEmpty: YES / Enveloped: NO / Isolate: SEROTYPE / Type: VIRION
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company
MicroscopyModel: FEI TECNAI ARCTICA
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 200 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1500 nm / Nominal defocus min: 500 nm
Image recordingElectron dose: 35.7 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k)

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Processing

SoftwareName: PHENIX / Version: 1.18.2_3874: / Classification: refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.23 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 12461 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0075017
ELECTRON MICROSCOPYf_angle_d0.6426838
ELECTRON MICROSCOPYf_dihedral_angle_d11.481666
ELECTRON MICROSCOPYf_chiral_restr0.045720
ELECTRON MICROSCOPYf_plane_restr0.005908

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