PMID- 30742069
OWN - NLM
STAT- MEDLINE
DCOM- 20190729
LR  - 20220416
IS  - 2058-5276 (Electronic)
IS  - 2058-5276 (Linking)
VI  - 4
IP  - 4
DP  - 2019 Apr
TI  - Adeno-associated virus 2 bound to its cellular receptor AAVR.
PG  - 675-682
LID - 10.1038/s41564-018-0356-7 [doi]
AB  - 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 A 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.
FAU - Zhang, Ran
AU  - Zhang R
AD  - MOE Laboratory of Protein Science and Collaborative Innovation Center of 
      Biotherapy, School of Medicine, Tsinghua University, Beijing, China.
AD  - School of Life Sciences, Tsinghua University, Beijing, China.
FAU - Cao, Lin
AU  - Cao L
AD  - MOE Laboratory of Protein Science and Collaborative Innovation Center of 
      Biotherapy, School of Medicine, Tsinghua University, Beijing, China.
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Life Science and 
      Pharmacy, Nankai University, Tianjin, China.
FAU - Cui, Mengtian
AU  - Cui M
AD  - Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Capital Medical University, Beijing, China.
FAU - Sun, Zixian
AU  - Sun Z
AD  - School of Life Sciences, Tsinghua University, Beijing, China.
FAU - Hu, Mingxu
AU  - Hu M
AUID- ORCID: 0000-0003-3603-3966
AD  - School of Life Sciences, Tsinghua University, Beijing, China.
FAU - Zhang, Rouxuan
AU  - Zhang R
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Life Science and 
      Pharmacy, Nankai University, Tianjin, China.
FAU - Stuart, William
AU  - Stuart W
AD  - Faculty of Biology, Medicine, and Health, University of Manchester, Manchester, 
      UK.
FAU - Zhao, Xiaochu
AU  - Zhao X
AD  - The Experimental High School Affiliated to Beijing Normal University, Beijing, 
      China.
FAU - Yang, Zirui
AU  - Yang Z
AD  - The High School Affiliated to Renmin University, Beijing, China.
FAU - Li, Xueming
AU  - Li X
AD  - School of Life Sciences, Tsinghua University, Beijing, China.
FAU - Sun, Yuna
AU  - Sun Y
AD  - National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy 
      of Science, Beijing, China.
FAU - Li, Shentao
AU  - Li S
AD  - Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Capital Medical University, Beijing, China.
FAU - Ding, Wei
AU  - Ding W
AUID- ORCID: 0000-0002-1664-3401
AD  - Department of Biochemistry and Molecular Biology, School of Basic Medical 
      Sciences, Capital Medical University, Beijing, China. weiding@ccmu.edu.cn.
FAU - Lou, Zhiyong
AU  - Lou Z
AUID- ORCID: 0000-0003-2728-881X
AD  - MOE Laboratory of Protein Science and Collaborative Innovation Center of 
      Biotherapy, School of Medicine, Tsinghua University, Beijing, China. 
      louzy@mail.tsinghua.edu.cn.
FAU - Rao, Zihe
AU  - Rao Z
AD  - MOE Laboratory of Protein Science and Collaborative Innovation Center of 
      Biotherapy, School of Medicine, Tsinghua University, Beijing, China.
AD  - School of Life Sciences, Tsinghua University, Beijing, China.
AD  - State Key Laboratory of Medicinal Chemical Biology, College of Life Science and 
      Pharmacy, Nankai University, Tianjin, China.
AD  - National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy 
      of Science, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190211
PL  - England
TA  - Nat Microbiol
JT  - Nature microbiology
JID - 101674869
RN  - 0 (Capsid Proteins)
RN  - 0 (KIAA0319L protein, human)
RN  - 0 (Receptors, Cell Surface)
RN  - Adeno-associated virus-2
MH  - Capsid/*metabolism/ultrastructure
MH  - Capsid Proteins/genetics/metabolism
MH  - Cell Line
MH  - Cryoelectron Microscopy
MH  - Dependovirus
MH  - Host-Parasite Interactions
MH  - Humans
MH  - Parvoviridae Infections/*virology
MH  - Parvovirinae/genetics/*metabolism/ultrastructure
MH  - Protein Binding
MH  - Protein Domains
MH  - Receptors, Cell Surface/chemistry/genetics/*metabolism/ultrastructure
EDAT- 2019/02/12 06:00
MHDA- 2019/07/30 06:00
CRDT- 2019/02/12 06:00
PHST- 2018/10/03 00:00 [received]
PHST- 2018/12/21 00:00 [accepted]
PHST- 2019/02/12 06:00 [pubmed]
PHST- 2019/07/30 06:00 [medline]
PHST- 2019/02/12 06:00 [entrez]
AID - 10.1038/s41564-018-0356-7 [pii]
AID - 10.1038/s41564-018-0356-7 [doi]
PST - ppublish
SO  - Nat Microbiol. 2019 Apr;4(4):675-682. doi: 10.1038/s41564-018-0356-7. Epub 2019 
      Feb 11.