6IHB

Adeno-Associated Virus 2 in complex with AAVR

Summary for 6IHB

• Entry DOI: 10.2210/pdb6ihb/pdb
• EMDB information: 9672
• Descriptor: Dyslexia-associated protein KIAA0319-like protein, Capsid protein VP1 (2 entities in total)
• Functional Keywords: aav2, virus
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 92345.80

Authors

Lou, Z.Y.,Zhang, R. (deposition date: 2018-09-29, release date: 2019-03-20, Last modification date: 2024-03-27)

Primary citation

Zhang, R.,Cao, L.,Cui, M.,Sun, Z.,Hu, M.,Zhang, R.,Stuart, W.,Zhao, X.,Yang, Z.,Li, X.,Sun, Y.,Li, S.,Ding, W.,Lou, Z.,Rao, Z.
Adeno-associated virus 2 bound to its cellular receptor AAVR.
Nat Microbiol, 4:675-682, 2019

PubMed 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 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.

PubMed: 30742069
DOI: 10.1038/s41564-018-0356-7

Experimental method

ELECTRON MICROSCOPY (2.84 Å)