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TitleAdeno-associated virus 2 bound to its cellular receptor AAVR.
Journal, issue, pagesNat Microbiol, Vol. 4, Issue 4, Page 675-682, Year 2019
Publish dateFeb 11, 2019
AuthorsRan 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 /
PubMed AbstractAdeno-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.
External linksNat Microbiol / PubMed:30742069
MethodsEM (single particle)
Resolution2.8 - 2.84 Å
Structure data

9671

6ih9

EMDB-9671, PDB-6ih9:
Adeno-Associated Virus 2 at 2.8 ang
Method: EM (single particle) / Resolution: 2.8 Å

9672

6ihb

EMDB-9672, PDB-6ihb:
Adeno-Associated Virus 2 in complex with AAVR
Method: EM (single particle) / Resolution: 2.84 Å

Source
  • adeno-associated virus 2 (isolate srivastava/1982)
  • homo sapiens (human)
KeywordsVIRUS / AAV2

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