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Open data
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Basic information
Entry | Database: PDB / ID: 7wqp | ||||||
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Title | Adeno-associated virus serotype PHP.eB in complex with AAVR | ||||||
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![]() | VIRUS / Adeno-associated virus serotype 9 / AAVR | ||||||
Function / homology | ![]() T=1 icosahedral viral capsid / neuron migration / cytoplasmic vesicle / Golgi membrane / nucleolus / structural molecule activity / Golgi apparatus / membrane / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.76 Å | ||||||
![]() | Xu, G. / Lou, Z. | ||||||
Funding support | 1items
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![]() | ![]() 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. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 122.2 KB | Display | ![]() |
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PDB format | ![]() | 93.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 32712MC ![]() 7wjwC ![]() 7wjxC ![]() 7wqoC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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3 | ![]()
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Symmetry | Point symmetry: (Schoenflies symbol: I (icosahedral)) |
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Components
#1: Protein | Mass: 10056.090 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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#2: Protein | Mass: 59205.293 Da / Num. of mol.: 1 / Mutation: A594F, Q595K Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
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Source (natural) |
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Source (recombinant) |
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Details of virus | Empty: YES / Enveloped: NO / Isolate: SEROTYPE / Type: VIRION | ||||||||||||||||||||||||
Natural host | Organism: Homo sapiens | ||||||||||||||||||||||||
Buffer solution | pH: 7.4 | ||||||||||||||||||||||||
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Microscopy | Model: FEI TECNAI ARCTICA |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 35.7 e/Å2 / Film or detector model: FEI FALCON III (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.76 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 16526 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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