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- EMDB-71278: Cryo-EM structure of AAV.CAP-B10 complexed to AAVR-PKD2 -

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Basic information

Entry
Database: EMDB / ID: EMD-71278
TitleCryo-EM structure of AAV.CAP-B10 complexed to AAVR-PKD2
Map datamain refinement map
Sample
  • Virus: CAP-B10 (virus)
    • Protein or peptide: Capsid protein VP1
    • Protein or peptide: Dyslexia-associated protein KIAA0319-like protein
KeywordsAAV / receptor / complex / liver detarget / VIRUS
Function / homology
Function and homology information


proacrosomal vesicle fusion / acrosome assembly / response to auditory stimulus / flagellated sperm motility / T=1 icosahedral viral capsid / receptor-mediated endocytosis of virus by host cell / trans-Golgi network / neuron migration / cytoplasmic vesicle / spermatogenesis ...proacrosomal vesicle fusion / acrosome assembly / response to auditory stimulus / flagellated sperm motility / T=1 icosahedral viral capsid / receptor-mediated endocytosis of virus by host cell / trans-Golgi network / neuron migration / cytoplasmic vesicle / spermatogenesis / Golgi membrane / nucleolus / structural molecule activity / Golgi apparatus / membrane / plasma membrane
Similarity search - Function
Dyslexia-associated protein KIAA0319-like / : / Dyslexia-associated protein KIAA0319 N-terminal domain / KIAA0319 C-terminal domain / MANSC domain / MANSC domain profile. / K319L-like, PKD domain / Polycystic kidney disease (PKD) domain profile. / PKD domain / PKD domain superfamily ...Dyslexia-associated protein KIAA0319-like / : / Dyslexia-associated protein KIAA0319 N-terminal domain / KIAA0319 C-terminal domain / MANSC domain / MANSC domain profile. / K319L-like, 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 VP1/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 / Mus musculus (house mouse) / CAP-B10 (virus)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.2 Å
AuthorsBrittain TJ / Jang S
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)DP1NS111369 United States
National Institutes of Health/National Institute of Mental Health (NIH/NIMH)UF1MH128336 United States
CitationJournal: Mol Ther / Year: 2026
Title: Structural basis of liver de-targeting and neuronal tropism of CNS-targeted AAV capsids.
Authors: Tyler J Brittain / Seongmin Jang / Gerard M Coughlin / Jonathan D Hoang / Bre'Anna H Barcelona / Izabela Giriat / Fiona Ristic / Nathan Appling / Camille P M A Chossis / Timothy F Shay / Viviana Gradinaru /
Abstract: Developing effective vectors for gene therapy requires accurate on-target coverage while minimizing off-target transduction that can lead to adverse events. In mice, the engineered capsid PHP.eB ...Developing effective vectors for gene therapy requires accurate on-target coverage while minimizing off-target transduction that can lead to adverse events. In mice, the engineered capsid PHP.eB shows enhanced brain transduction, while the further engineered CAP-B10 is also de-targeted from astrocytes and liver. Here, we solved cryoelectron microscopy (cryo-EM) structures of CAP-B10 and its complex with the adeno-associated virus receptor (AAVR) domain PKD2, at 2.22- and 2.20-Å resolutions, respectively. These structures reveal a motif that hinders AAVR binding, which we confirmed by measuring affinities. We showed that this motif is transferable to other capsids by solving cryo-EM structures of AAV9-X1, at 3.09 Å, and AAV9-X1.1 without and with PKD2, at 2.51 and 2.18 Å, respectively. Using this structural information, we designed and validated novel AAV variants with reduced liver and altered brain cell tropism in vivo. Overall, we provide a framework for using structural information to guide rational engineering of gene delivery vectors to achieve safe and effective delivery.
History
DepositionJun 17, 2025-
Header (metadata) releaseApr 15, 2026-
Map releaseApr 15, 2026-
UpdateMay 20, 2026-
Current statusMay 20, 2026Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_71278.png

Downloads & links

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Map

FileDownload / File: emd_71278.map.gz / Format: CCP4 / Size: 325 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Annotationmain refinement map
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.86 Å/pix.
x 440 pix.
= 376.2 Å		0.86 Å/pix.
x 440 pix.
= 376.2 Å		0.86 Å/pix.
x 440 pix.
= 376.2 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.855 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.065
Minimum - Maximum-0.16440149 - 0.4734902
Average (Standard dev.)0.009075093 (±0.039727364)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions440440440
Spacing440440440
CellA=B=C: 376.2 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: Halfmap A

Fileemd_71278_half_map_1.map
AnnotationHalfmap A
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: Halfmap B

Fileemd_71278_half_map_2.map
AnnotationHalfmap B
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : CAP-B10

EntireName: CAP-B10 (virus)
Components
  • Virus: CAP-B10 (virus)
    • Protein or peptide: Capsid protein VP1
    • Protein or peptide: Dyslexia-associated protein KIAA0319-like protein

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Supramolecule #1: CAP-B10

SupramoleculeName: CAP-B10 / type: virus / ID: 1 / Parent: 0 / Macromolecule list: all / NCBI-ID: 235455 / Sci species name: CAP-B10 / Virus type: VIRION / Virus isolate: SEROTYPE / Virus enveloped: No / Virus empty: No

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Macromolecule #1: Capsid protein VP1

MacromoleculeName: Capsid protein VP1 / type: protein_or_peptide / ID: 1 / Details: CAP-B10 VP1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Adeno-associated virus
Molecular weightTheoretical: 82.161648 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MAADGYLPDW LEDNLSEGIR EWWALKPGAP QPKANQQHQD NARGLVLPGY KYLGPGNGLD KGEPVNAADA AALEHDKAYD QQLKAGDNP YLKYNHADAE FQERLKEDTS FGGNLGRAVF QAKKRLLEPL GLVEEAAKTA PGKKRPVEQS PQEPDSSAGI G KSGAQPAK ...String:
MAADGYLPDW LEDNLSEGIR EWWALKPGAP QPKANQQHQD NARGLVLPGY KYLGPGNGLD KGEPVNAADA AALEHDKAYD QQLKAGDNP YLKYNHADAE FQERLKEDTS FGGNLGRAVF QAKKRLLEPL GLVEEAAKTA PGKKRPVEQS PQEPDSSAGI G KSGAQPAK KRLNFGQTGD TESVPDPQPI GEPPAAPSGV GSLTMASGGG APVADNNEGA DGVGSSSGNW HCDSQWLGDR VI TTSTRTW ALPTYNNHLY KQISNSTSGG SSNDNAYFGY STPWGYFDFN RFHCHFSPRD WQRLINNNWG FRPKRLNFKL FNI QVKEVT DNNGVKTIAN NLTSTVQVFT DSDYQLPYVL GSAHEGCLPP FPADVFMIPQ YGYLTLNDGS QAVGRSSFYC LEYF PSQML RTGNNFQFSY EFENVPFHSS YAHSQSLDRL MNPLIDQYLY YLSKTIDGAA TKNQTLKFSV AGPSNMAVQG RNYIP GPSY RQQRVSTTVT QNNNSEFAWP GASSWALNGR NSLMNPGPAM ASHKEGEDRF FPLSGSLIFG KQGTGRDNVD ADKVMI TNE EEIKTTNPVA TESYGQVATN HQSDGTLAVP FKAQAQTGWV QNQGILPGMV WQDRDVYLQG PIWAKIPHTD GNFHPSP LM GGFGMKHPPP QILIKNTPVP ADPPTAFNKD KLNSFITQYS TGQVSVEIEW ELQKENSKRW NPEIQYTSNY YKSNNVEF A VNTEGVYSEP RPIGTRYLTR NL

UniProtKB: Capsid protein VP1

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Macromolecule #2: Dyslexia-associated protein KIAA0319-like protein

MacromoleculeName: Dyslexia-associated protein KIAA0319-like protein / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Mus musculus (house mouse)
Molecular weightTheoretical: 13.587939 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
PRKNRPPVAV VSPQFQEISL PTTSTIIDGS QSTDDDKIVQ YHWEELKGPL REEKISEDTA ILKLSKLVPG NYTFSLTVVD SDGATNSTT ASLTVNKAVD YPPGGSEQKL ISEEDLGGSH HHHHH

UniProtKB: Dyslexia-associated protein KIAA0319-like 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

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS 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: 4.0 µm / Nominal defocus min: 2.0 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: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.2 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 65563
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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