The Structural Basis for the Integrity of Adenovirus Ad3 Dodecahedron
| Autor: | Guy Schoehn, Monika Zochowska, Barbara Nerlo, Antonina Naskalska, Chloe Zubieta, Jadwiga Chroboczek, Ewa Szolajska, Pascal Fender, I. O. Andreev, Stephen Cusack, Jean-Pierre Andrieu, Wim P. Burmeister |
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| Přispěvatelé: | Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), European Molecular Biology Laboratory, European Molecular Biology Laboratory [Grenoble] (EMBL), TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Macromolecular Assemblies
[SDV.BIO]Life Sciences [q-bio]/Biotechnology MESH: Sequence Homology Amino Acid viruses lcsh:Medicine MESH: Protein Structure Secondary MESH: Amino Acid Sequence medicine.disease_cause Crystallography X-Ray Biochemistry Protein Structure Secondary Nanotechnology [INFO.INFO-BT]Computer Science [cs]/Biotechnology lcsh:Science Site-directed mutagenesis Peptide sequence MESH: Capsid Proteins Genetics 0303 health sciences Multidisciplinary Chemistry 030302 biochemistry & molecular biology 3. Good health Subviral Particles MESH: Mutagenesis Site-Directed Capsid Structural Proteins Research Article Biotechnology MESH: Adenoviruses Human Protein Structure Viral protein Protein domain Materials Science Molecular Sequence Data Biophysics Gene delivery Viral Structure Microbiology 03 medical and health sciences Virology Viruslike Particles medicine Humans Amino Acid Sequence Biology 030304 developmental biology MESH: Humans MESH: Molecular Sequence Data Sequence Homology Amino Acid Adenoviruses Human lcsh:R Proteins MESH: Crystallography X-Ray Dodecameric protein Membrane protein Bionanotechnology Mutagenesis Site-Directed lcsh:Q Capsid Proteins |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2012, 7 (9), pp.e46075. ⟨10.1371/journal.pone.0046075⟩ PLoS ONE, 2012, 7 (9), pp.e46075. ⟨10.1371/journal.pone.0046075⟩ PLoS ONE, Vol 7, Iss 9, p e46075 (2012) |
| ISSN: | 1932-6203 |
| Popis: | International audience; During the viral life cycle adenoviruses produce excess capsid proteins. Human adenovirus serotype 3 (Ad3) synthesizes predominantly an excess of free pentons, the complexes of pentameric penton base and trimeric fiber proteins, which are responsible for virus penetration. In infected cells Ad3 pentons spontaneously assemble into dodecahedral virus-like nano-particles containing twelve pentons. They also form in insect cells during expression in the baculovirus system. Similarly, in the absence of fiber protein dodecahedric particles built of 12 penton base pentamers can be produced. Both kinds of dodecahedra show remarkable efficiency of intracellular penetration and can be engineered to deliver several millions of foreign cargo molecules to a single target cell. For this reason, they are of great interest as a delivery vector. In order to successfully manipulate this potential vector for drug and/or gene delivery, an understanding of the molecular basis of vector assembly and integrity is critical. Crystallographic data in conjunction with site-directed mutagenesis and biochemical analysis provide a model for the molecular determinants of dodecamer particle assembly and the requirements for stability. The 3.8 Å crystal structure of Ad3 penton base dodecamer (Dd) shows that the dodecahedric structure is stabilized by strand-swapping between neighboring penton base molecules. Such N-terminal strand-swapping does not occur for Dd of Ad2, a serotype which does not form Dd under physiological conditions. This unique stabilization of the Ad3 dodecamer is controlled by residues 59-61 located at the site of strand switching, the residues involved in putative salt bridges between pentamers and by the disordered N-terminus (residues 1-47), as confirmed by site directed mutagenesis and biochemical analysis of mutant and wild type protein. We also provide evidence that the distal N-terminal residues are externally exposed and available for attaching cargo. |
| Databáze: | OpenAIRE |
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