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Open data
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Basic information
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Title | Adeno-associated virus serotype PHP.eB in complex with AAVR | |||||||||
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![]() | Adeno-associated virus serotype 9 / AAVR / VIRUS | |||||||||
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 | single particle reconstruction / cryo EM / Resolution: 3.76 Å | |||||||||
![]() | Xu G / Lou Z | |||||||||
Funding support | 1 items
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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. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 50.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 11.3 KB 11.3 KB | Display Display | ![]() |
Images | ![]() | 63 KB | ||
Filedesc metadata | ![]() | 5.4 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7wqpMC ![]() 7wjwC ![]() 7wjxC ![]() 7wqoC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 0.932 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : Adeno-associated virus 9
Entire | Name: ![]() ![]() |
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Components |
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-Supramolecule #1: Adeno-associated virus 9
Supramolecule | Name: Adeno-associated virus 9 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: Dyslexia-associated protein KIAA0319-like protein
Supramolecule | Name: Dyslexia-associated protein KIAA0319-like protein / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Supramolecule #3: Adeno-associated virus 9
Supramolecule | Name: Adeno-associated virus 9 / type: virus / ID: 3 / Parent: 1 / Macromolecule list: #2 / NCBI-ID: 235455 / Sci species name: Adeno-associated virus 9 / Virus type: VIRION / Virus isolate: SEROTYPE / Virus enveloped: No / Virus empty: Yes |
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-Macromolecule #1: Dyslexia-associated protein KIAA0319-like protein
Macromolecule | Name: Dyslexia-associated protein KIAA0319-like protein / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 10.05609 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: NRPPIAIVSP QFQEISLPTT STVIDGSQST DDDKIVQYHW EELKGPLREE KISEDTAILK LSKLVPGNYT FSLTVVDSDG ATNSTTANL TVN UniProtKB: Dyslexia-associated protein KIAA0319-like protein |
-Macromolecule #2: Capsid protein VP1
Macromolecule | Name: Capsid protein VP1 / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 59.205293 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DGVGSSSGNW HCDSQWLGDR VITTSTRTWA LPTYNNHLYK QISNSTSGGS SNDNAYFGYS TPWGYFDFNR FHCHFSPRDW QRLINNNWG FRPKRLNFKL FNIQVKEVTD NNGVKTIANN LTSTVQVFTD SDYQLPYVLG SAHEGCLPPF PADVFMIPQY G YLTLNDGS ...String: DGVGSSSGNW HCDSQWLGDR VITTSTRTWA LPTYNNHLYK QISNSTSGGS SNDNAYFGYS TPWGYFDFNR FHCHFSPRDW QRLINNNWG FRPKRLNFKL FNIQVKEVTD NNGVKTIANN LTSTVQVFTD SDYQLPYVLG SAHEGCLPPF PADVFMIPQY G YLTLNDGS QAVGRSSFYC LEYFPSQMLR TGNNFQFSYE FENVPFHSSY AHSQSLDRLM NPLIDQYLYY LSKTINGSGQ NQ QTLKFSV AGPSNMAVQG RNYIPGPSYR QQRVSTTVTQ NNNSEFAWPG ASSWALNGRN SLMNPGPAMA SHKEGEDRFF PLS GSLIFG KQGTGRDNVD ADKVMITNEE EIKTTNPVAT ESYGQVATNH QSDGTLAVPF KAQAQTGWVQ NQGILPGMVW QDRD VYLQG PIWAKIPHTD GNFHPSPLMG GFGMKHPPPQ ILIKNTPVPA DPPTAFNKDK LNSFITQYST GQVSVEIEWE LQKEN SKRW NPEIQYTSNY YKSNNVEFAV NTEGVYSEPR PIGTRYLTRN L UniProtKB: Capsid protein VP1 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TECNAI ARCTICA |
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Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Average electron dose: 35.7 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.76 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 16526 |
Initial angle assignment | Type: ANGULAR RECONSTITUTION |
Final angle assignment | Type: ANGULAR RECONSTITUTION |