Institut de Biologie Structurale (IBS), Université Grenoble Alpes, CNRS, CEA, 71 Avenue des Martyrs, 38042, Grenoble, France.
Laboratoire de Physiologie Cellulaire et Végétale, Biosciences and Biotechnology Institute of Grenoble, UMR5168, CNRS/CEA/INRA/UGA, 17 Rue des Martyrs, 38054, Grenoble, France.
Nat Commun. 2019 Mar 12;10(1):1181. doi: 10.1038/s41467-019-09220-y.
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.
人腺病毒（HAd）与宿主细胞的附着是感染的关键步骤。最初的附着通过腺病毒纤维扣状蛋白和细胞受体发生。在这里，我们报告了一个由三聚体 HAd 型 3 纤维扣（HAd3K）和人桥粒芯糖蛋白 2（DSG2）组成的 <100 kDa 非对称复合物的低温电子显微镜（cryo-EM）结构。该结构显示了以前在其他 HAd-受体复合物中未观察到的独特的 1:1 和 2:1（DSG2：扣状三聚体）的比例。我们证明，纤维扣状蛋白中 Asp261 的突变足以完全消除受体结合。这些数据为腺病毒感染策略提供了新的见解，并为腺病毒载体的开发和基于结构的设计提供了思路。
