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

Emilie Vassal-Stermann (1) , Grégory Effantin (1) , Chloe Zubieta (2) , Wim P Burmeister (1) , Frédéric Iseni (3) , Hongjie Wang (4) , André Lieber (5) , Guy Schoehn (1) , Pascal Fender (1)

1 IBS - UMR 5075 - Institut de biologie structurale
2 StructDev - StructDev
3 Unité de Virologie
4 Department of Medicine, Division of Medical Genetics
5 Division of Medical Genetics [Seattle]

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.

Domaines: Biologie structurale [q-bio.BM]

Emilie Vassal-Stermann, Grégory Effantin, Chloe Zubieta, Wim P Burmeister, Frédéric Iseni, et al.. CryoEM structure of adenovirus type 3 fibre with desmoglein 2 shows an unusual mode of receptor engagement. Nature Communications, 2019, 10 (1), pp.1181. ⟨10.1038/s41467-019-09220-y⟩. ⟨hal-02085944⟩