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Adeno-associated virus 2 bound to its cellular receptor AAVR

本站小编 Free考研/2020-04-17

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Adeno-associated virus 2 bound to its cellular receptor AAVR
文献类型:期刊
通讯作者:Lou, ZY (reprint author), Tsinghua Univ, MOE Lab Prot Sci, Beijing, Peoples R China.; Lou, ZY (reprint author), Tsinghua Univ, Collaborat Innovat Ctr Biotherapy, Sch Med, Beijing, Peoples R China.; Ding, W (reprint author), Capital Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing, Peoples R China.
期刊名称:NATURE MICROBIOLOGY
年:2019
卷:4
期:4
页码:675-682
ISSN:2058-5276
摘要: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 angstrom resolution. This structure reveals that of the five Ig-like polycystic kidney disease (PKD) domains in AAVR, PKD2 bind ...More
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 angstrom 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. ...Hide

DOI:10.1038/s41564-018-0356-7
百度学术:Adeno-associated virus 2 bound to its cellular receptor AAVR
语言:外文
被引频次:
11
人气指数:2
浏览次数:2
基金:National Program on Key Research Project of China [2017YFC0840300, 2018YFA0507200]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81322023, 31770309, 81372284, 81520108019, 31370733]
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