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CryoEM structure of adenovirus type 3 fibre with desmoglein 2 shows an unusual mode of receptor engagement. | LitMetric

AI Article Synopsis

  • The study focuses on how human adenovirus (HAd) attaches to host cells, which is a key step in infection, involving the adenoviral fiber knob protein and a receptor called desmoglein 2 (DSG2).
  • Using cryo-electron microscopy, researchers analyzed a complex formed by the HAd type 3 fiber knob and DSG2, revealing a unique binding arrangement not seen before in similar interactions.
  • The research discovered that a specific mutation in the fiber knob can completely prevent the virus from binding to the receptor, offering valuable insights for future adenoviral vector development and targeted treatments.

Article Abstract

Attachment of human adenovirus (HAd) to the host cell is a critical step of infection. Initial attachment occurs via the adenoviral fibre knob protein and a cellular receptor. Here we report the cryo-electron microscopy (cryo-EM) structure of a <100 kDa non-symmetrical complex comprising the trimeric HAd type 3 fibre knob (HAd3K) and human desmoglein 2 (DSG2). The structure reveals a unique stoichiometry of 1:1 and 2:1 (DSG2: knob trimer) not previously observed for other HAd-receptor complexes. We demonstrate that mutating Asp261 in the fibre knob is sufficient to totally abolish receptor binding. These data shed new light on adenovirus infection strategies and provide insights for adenoviral vector development and structure-based design.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414520PMC
http://dx.doi.org/10.1038/s41467-019-09220-yDOI Listing

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