Conserved Fiber-Penton Base Interaction Revealed by Nearly Atomic Resolution Cryo-Electron Microscopy of the Structure of Adenovirus Provides Insight into Receptor Interaction |
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| Authors: | Changchun Cao Xiaoyan Dong Xiaobing Wu Boyun Wen Gang Ji Lingpeng Cheng Hongrong Liu |
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| Affiliation: | aCollege of Physics and Information Science and Key Laboratory of Low-dimensional Quantum Structures and Quantum Control of the Ministry of Education, Hunan Normal University, Changsha, Hunan, China;bBeijing FivePlus Molecular Medicine Institute, Beijing, China;cNational Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China |
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| Abstract: | Adenovirus (Ad) cell attachment is initiated by the attachment of the fiber protein to a primary receptor (usually CAR or CD46). This event is followed by the engagement of the penton base protein with a secondary receptor (integrin) via its loop region, which contains an Arg-Gly-Asp (RGD) motif, to trigger virus internalization. To understand the well-orchestrated adenovirus cell attachment process that involves the fiber and the penton base, we reconstructed the structure of an Ad5F35 capsid, comprising an adenovirus type 5 (Ad5) capsid pseudotyped with an Ad35 fiber, at a resolution of approximately 4.2 Å. The fiber-penton base interaction in the cryo-electron microscopic (cryo-EM) structure of Ad5F35 is similar to that in the cryo-EM structure of Ad5, indicating that the fiber-penton base interaction of adenovirus is conserved. Our structure also confirms that the C-terminal segment of the fiber tail domain constitutes the bottom trunk of the fiber shaft. Based on the conserved fiber-penton base interaction, we have proposed a model for the interaction of Ad5F35 with its primary and secondary receptors. This model could provide insight for designing adenovirus gene delivery vectors. |
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