Journal: Nat Microbiol / Year: 2019 Title: Adeno-associated virus 2 bound to its cellular receptor AAVR. Authors: Ran 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 / Abstract: 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 ...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.
History
Deposition
Sep 29, 2018
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Header (metadata) release
Mar 20, 2019
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Map release
Mar 20, 2019
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Update
Mar 27, 2024
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Current status
Mar 27, 2024
Processing site: PDBj / Status: Released
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