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Proc Natl Acad Sci U S A. 2014 Jun 17;111(24):8815-9. doi: 10.1073/pnas.1404575111. Epub 2014 Jun 2.

Single-particle EM reveals plasticity of interactions between the adenovirus penton base and integrin αVβ3.

Author information

1
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037;
2
Interfaculty Institute of Biochemistry, University of Tuebingen, D-72076 Tuebingen, Germany;
3
Department of Physical Chemistry, University of Freiburg, D-79104 Freiburg, Germany; and.
4
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.
5
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037; thilo.stehle@uni-tuebingen.de jackj@scripps.edu.

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.

PMID:
24889614
PMCID:
PMC4066496
DOI:
10.1073/pnas.1404575111
[Indexed for MEDLINE]
Free PMC Article

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