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Divergent engagements between adeno-associated viruses with their cellular receptor AAVR

Author

Listed:
  • Ran Zhang

    (Tsinghua University
    Tsinghua University)

  • Guangxue Xu

    (Tsinghua University)

  • Lin Cao

    (Nankai University)

  • Zixian Sun

    (Tsinghua University)

  • Yong He

    (Nankai University)

  • Mengtian Cui

    (Capital Medical University)

  • Yuna Sun

    (Chinese Academy of Science)

  • Shentao Li

    (Capital Medical University)

  • Huapeng Li

    (PackGene Biotech)

  • Lan Qin

    (DIAN Diagnostics)

  • Mingxu Hu

    (Tsinghua University)

  • Zhengjia Yuan

    (High School Attached to Capital Normal University)

  • Zipei Rao

    (No. 4 High School)

  • Wei Ding

    (Capital Medical University)

  • Zihe Rao

    (Tsinghua University
    Tsinghua University
    Nankai University
    Chinese Academy of Science)

  • Zhiyong Lou

    (Tsinghua University)

Abstract

Adeno-associated virus (AAV) receptor (AAVR) is an essential receptor for the entry of multiple AAV serotypes with divergent rules; however, the mechanism remains unclear. Here, we determine the structures of the AAV1-AAVR and AAV5-AAVR complexes, revealing the molecular details by which PKD1 recognizes AAV5 and PKD2 is solely engaged with AAV1. PKD2 lies on the plateau region of the AAV1 capsid. However, the AAV5-AAVR interface is strikingly different, in which PKD1 is bound at the opposite side of the spike of the AAV5 capsid than the PKD2-interacting region of AAV1. Residues in strands F/G and the CD loop of PKD1 interact directly with AAV5, whereas residues in strands B/C/E and the BC loop of PKD2 make contact with AAV1. These findings further the understanding of the distinct mechanisms by which AAVR recognizes various AAV serotypes and provide an example of a single receptor engaging multiple viral serotypes with divergent rules.

Suggested Citation

  • Ran Zhang & Guangxue Xu & Lin Cao & Zixian Sun & Yong He & Mengtian Cui & Yuna Sun & Shentao Li & Huapeng Li & Lan Qin & Mingxu Hu & Zhengjia Yuan & Zipei Rao & Wei Ding & Zihe Rao & Zhiyong Lou, 2019. "Divergent engagements between adeno-associated viruses with their cellular receptor AAVR," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11668-x
    DOI: 10.1038/s41467-019-11668-x
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