title: Distribution of DNA-condensing protein complexes in the adenovirus core.
abstract: Genome packing in adenovirus has long evaded precise description, since the viral dsDNA molecule condensed by proteins (core) lacks icosahedral order characteristic of the virus protein coating (capsid). We show that useful insights regarding the organization of the core can be inferred from the analysis of spatial distributions of the DNA and condensing protein units (adenosomes). These were obtained from the inspection of cryo-electron tomography reconstructions of individual human adenovirus particles. Our analysis shows that the core lacks symmetry and strict order, yet the adenosome distribution is not entirely random. The features of the distribution can be explained by modeling the condensing proteins and the part of the genome in each adenosome as very soft spheres, interacting repulsively with each other and with the capsid, producing a minimum outward pressure of ∼0.06 atm. Although the condensing proteins are connected by DNA in disrupted virion cores, in our models a backbone of DNA linking the adenosomes is not required to explain the experimental results in the confined state. In conclusion, the interior of an adenovirus infectious particle is a strongly confined and dense phase of soft particles (adenosomes) without a strictly defined DNA backbone.
authors.affiliation: Department of Macromolecular Structures, Centro Nacional de Biotecnología (CNB-CSIC), 28049 Madrid, Spain NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB-CSIC), 28049 Madrid, Spain.
authors.forename: Ana J
authors.initials: AJ
authors.lastname: Pérez-Berná
authors.affiliation: Institute of Physics, Bijenička cesta 46, HR-10000 Zagreb, Croatia.
authors.forename: Sanjin
authors.initials: S
authors.lastname: Marion
authors.affiliation: Department of Macromolecular Structures, Centro Nacional de Biotecnología (CNB-CSIC), 28049 Madrid, Spain NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB-CSIC), 28049 Madrid, Spain.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Chichón
authors.affiliation: Department of Macromolecular Structures, Centro Nacional de Biotecnología (CNB-CSIC), 28049 Madrid, Spain.
authors.forename: José J
authors.initials: JJ
authors.lastname: Fernández
authors.affiliation: Laboratory of Structural Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 20892, USA.
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Winkler
authors.affiliation: Department of Macromolecular Structures, Centro Nacional de Biotecnología (CNB-CSIC), 28049 Madrid, Spain NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB-CSIC), 28049 Madrid, Spain.
authors.forename: José L
authors.initials: JL
authors.lastname: Carrascosa
authors.affiliation: Laboratory of Structural Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), NIH, Bethesda, MD 20892, USA.
authors.forename: Alasdair C
authors.initials: AC
authors.lastname: Steven
authors.affiliation: Institute of Physics, Bijenička cesta 46, HR-10000 Zagreb, Croatia Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana, Slovenia asiber@ifs.hr.
authors.forename: Antonio
authors.initials: A
authors.lastname: Šiber
authors.affiliation: Department of Macromolecular Structures, Centro Nacional de Biotecnología (CNB-CSIC), 28049 Madrid, Spain NanoBiomedicine Initiative, Centro Nacional de Biotecnología (CNB-CSIC), 28049 Madrid, Spain carmen@cnb.csic.es.
authors.forename: Carmen
authors.identifier: http://orcid.org/0000-0001-9799-175X
authors.initials: C
authors.lastname: San Martín
mesh_terms: D000256:Adenoviridae / Q000648:ultrastructure*; D004279:DNA, Viral / Q000648:ultrastructure*; D055032:Electron Microscope Tomography; D056004:Molecular Dynamics Simulation; D014758:Viral Core Proteins / Q000648:ultrastructure*; D014771:Virion / Q000648:ultrastructure*
chemical_list: D004279:DNA, Viral; D014758:Viral Core Proteins
references.citation: Nucleic Acids Res. 1986 Mar 25;14(6):2721-35
references.pmid: 3960731
references.citation: Biochim Biophys Acta. 1982 Jan 26;696(1):76-86
references.pmid: 7082670
references.citation: Nucleic Acids Res. 2013 Feb 1;41(3):1569-80
references.pmid: 23258701
references.citation: Subcell Biochem. 2013;68:361-94
references.pmid: 23737058
references.citation: J Virol. 2011 Jan;85(1):481-96
references.pmid: 21047958
references.citation: Nat Protoc. 2008;3(6):977-90
references.pmid: 18536645
references.citation: J Virol. 2009 Feb;83(4):2025-8
references.pmid: 19036812
references.citation: J Mol Biol. 1986 Mar 5;188(1):23-37
references.pmid: 3712442
references.citation: J Virol. 1984 Jul;51(1):52-6
references.pmid: 6726895
references.citation: Nat Rev Mol Cell Biol. 2014 Jul;15(7):431
references.pmid: 24871800
references.citation: Viruses. 2012 May;4(5):847-77
references.pmid: 22754652
references.citation: J Mol Biol. 2009 Sep 18;392(2):547-57
references.pmid: 19563809
references.citation: Curr Opin Biotechnol. 1997 Feb;8(1):65-9
references.pmid: 9013656
references.citation: Proc Natl Acad Sci U S A. 1975 May;72(5):1843-7
references.pmid: 168578
references.citation: Biochim Biophys Acta. 1993 Nov 16;1216(2):175-85
references.pmid: 8241257
references.citation: J Virol. 1985 Nov;56(2):439-48
references.pmid: 4057357
references.citation: J Comput Chem. 2004 Oct;25(13):1605-12
references.pmid: 15264254
references.citation: Chem Rev. 2014 Mar 12;114(5):2733-58
references.pmid: 24364729
references.citation: Cell. 1991 Mar 8;64(5):1007-15
references.pmid: 1848156
references.citation: J Mol Biol. 1983 Jun 15;167(1):119-32
references.pmid: 6864797
references.citation: Science. 2010 Aug 27;329(5995):1038-43
references.pmid: 20798312
references.citation: J Virol. 2002 Feb;76(3):1100-8
references.pmid: 11773386
references.citation: Virology. 1968 Sep;36(1):115-25
references.pmid: 5669982
references.citation: J Virol. 1993 Oct;67(10):5911-21
references.pmid: 8371349
references.citation: J Virol. 1985 Aug;55(2):379-86
references.pmid: 4020954
references.citation: J Virol. 2014 Aug;88(16):9287-96
references.pmid: 24899200
references.citation: PLoS One. 2012;7(4):e36045
references.pmid: 22540018
references.citation: Structure. 2001 Oct;9(10):917-30
references.pmid: 11591347
references.citation: Nat Rev Genet. 2003 May;4(5):346-58
references.pmid: 12728277
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):19123-7
references.pmid: 17146053
references.citation: Structure. 2009 Dec 9;17(12):1563-1572
references.pmid: 20004160
references.citation: Phys Chem Chem Phys. 2012 Mar 21;14(11):3746-65
references.pmid: 22143065
references.citation: J Biol Chem. 2014 Apr 18;289(16):11421-11430
references.pmid: 24591515
references.citation: Curr Biol. 2012 Dec 18;22(24):2303-12
references.pmid: 23159597
references.citation: J Virol. 1983 Jun;46(3):749-55
references.pmid: 6304339
references.citation: Environ Microbiol. 2011 Jun;13(6):1454-66
references.pmid: 21392201
references.citation: J Struct Biol. 2008 Mar;161(3):232-42
references.pmid: 17869539
references.citation: Nucleic Acids Res. 2012 Mar;40(6):2369-76
references.pmid: 22116065
references.citation: J Cell Sci. 2007 May 1;120(Pt 9):1673-80
references.pmid: 17430977
references.citation: J Cell Biol. 2006 Dec 4;175(5):681-6
references.pmid: 17145959
references.citation: J Virol. 2004 Jun;78(12):6459-68
references.pmid: 15163739
references.citation: J Mol Biol. 2007 Mar 2;366(4):1142-60
references.pmid: 17208253
references.citation: Proc Natl Acad Sci U S A. 1976 Feb;73(2):401-4
references.pmid: 1061143
references.citation: Curr Opin Cell Biol. 2010 Jun;22(3):291-7
references.pmid: 20346642
references.citation: Nat Rev Microbiol. 2008 Dec;6(12):941-8
references.pmid: 19008892
references.citation: Proc Natl Acad Sci U S A. 1988 Jan;85(2):422-6
references.pmid: 2829185
references.citation: J Struct Biol. 2005 Oct;152(1):36-51
references.pmid: 16182563
references.citation: Virology. 2006 Aug 1;351(2):291-302
references.pmid: 16678874
references.citation: Biopolymers. 2007 Feb 5;85(2):115-30
references.pmid: 17103419
references.citation: Phys Rev Lett. 2007 Mar 23;98(12):128303
references.pmid: 17501165
references.citation: Adv Protein Chem. 2003;64:219-58
references.pmid: 13677049
references.citation: Nucleic Acids Res. 1983 Jan 25;11(2):441-60
references.pmid: 6828374
references.citation: Crit Rev Biochem Mol Biol. 2008 Nov-Dec;43(6):393-418
references.pmid: 19037758
references.citation: J Virol. 1975 Aug;16(2):366-87
references.pmid: 1152144
references.citation: Virology. 1975 Sep;67(1):197-208
references.pmid: 808902
references.citation: J Biol Chem. 2013 Jan 18;288(3):2092-102
references.pmid: 23043138
references.citation: Virology. 1989 Oct;172(2):506-12
references.pmid: 2800334
references.citation: Nucleic Acids Res. 1989 May 11;17(9):3535-50
references.pmid: 2726486
references.citation: J Struct Biol. 1996 Jan-Feb;116(1):71-6
references.pmid: 8742726
references.citation: Bioinformatics. 2011 Feb 15;27(4):582-3
references.pmid: 21172911
references.citation: J Phys Condens Matter. 2015 Feb 18;27(6):060301
references.pmid: 25563698
references.citation: J Am Chem Soc. 2013 Jul 31;135(30):11216-21
references.pmid: 23829592
references.citation: J Biol Chem. 2012 Sep 7;287(37):31582-95
references.pmid: 22791715
references.citation: J Struct Biol. 2001 Sep;135(3):239-50
references.pmid: 11722164