title: Conserved fiber-penton base interaction revealed by nearly atomic resolution cryo-electron microscopy of the structure of adenovirus provides insight into receptor interaction.
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.
authors.affiliation: College 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.
authors.forename: Changchun
authors.initials: C
authors.lastname: Cao
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Dong
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wu
authors.forename: Boyun
authors.initials: B
authors.lastname: Wen
authors.forename: Gang
authors.initials: G
authors.lastname: Ji
authors.forename: Lingpeng
authors.initials: L
authors.lastname: Cheng
authors.forename: Hongrong
authors.initials: H
authors.lastname: Liu
mesh_terms: D000256:Adenoviridae / Q000648:ultrastructure*; D000595:Amino Acid Sequence; D002213:Capsid / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D020285:Cryoelectron Microscopy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D021621:Imaging, Three-Dimensional; D016023:Integrins / Q000378:metabolism; D051916:Membrane Cofactor Protein / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D016023:Integrins; D051916:Membrane Cofactor Protein