title: Single-particle EM reveals plasticity of interactions between the adenovirus penton base and integrin αVβ3.
abstract: Human adenoviruses are double-stranded DNA viruses responsible for numerous infections, some of which can be fatal. Furthermore, adenoviruses are currently used in clinical trials as vectors for gene therapy applications. Although initial binding of adenoviruses to host attachment receptors has been extensively characterized, the interactions with the entry receptor (integrins) remain poorly understood at the structural level. We characterized the interactions between the adenovirus 9 penton base subunit and αVβ3 integrin using fluorescence correlation spectroscopy and single-particle electron microscopy to understand the mechanisms underlying virus internalization and infection. Our results indicate that the penton base subunit can bind integrins with high affinity and in several different orientations. These outcomes correlate with the requirement of the pentameric penton base to simultaneously bind several integrins to enable their clustering and promote virus entry into the host cell.
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037;
authors.forename: David
authors.initials: D
authors.lastname: Veesler
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tuebingen, D-72076 Tuebingen, Germany;
authors.forename: Karolina
authors.initials: K
authors.lastname: Cupelli
authors.affiliation: Department of Physical Chemistry, University of Freiburg, D-79104 Freiburg, Germany; and.
authors.forename: Markus
authors.initials: M
authors.lastname: Burger
authors.affiliation: Department of Physical Chemistry, University of Freiburg, D-79104 Freiburg, Germany; and.
authors.forename: Peter
authors.initials: P
authors.lastname: Gräber
authors.affiliation: Interfaculty Institute of Biochemistry, University of Tuebingen, D-72076 Tuebingen, Germany;Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232 thilo.stehle@uni-tuebingen.de jackj@scripps.edu.
authors.forename: Thilo
authors.initials: T
authors.lastname: Stehle
authors.affiliation: Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037; thilo.stehle@uni-tuebingen.de jackj@scripps.edu.
authors.forename: John E
authors.initials: JE
authors.lastname: Johnson
mesh_terms: D000260:Adenoviruses, Human; D002213:Capsid / Q000737:chemistry; D036022:Capsid Proteins / Q000737:chemistry*; D016000:Cluster Analysis; D005822:Genetic Vectors; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000737:chemistry*; D008024:Ligands; D008854:Microscopy, Electron; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D013050:Spectrometry, Fluorescence; D053586:Virus Internalization
chemical_list: D036022:Capsid Proteins; D039302:Integrin alphaVbeta3; D008024:Ligands; C043322:penton protein, adenovirus