title: Atomic structure of human adenovirus by cryo-EM reveals interactions among protein networks.
abstract: Construction of a complex virus may involve a hierarchy of assembly elements. Here, we report the structure of the whole human adenovirus virion at 3.6 angstroms resolution by cryo-electron microscopy (cryo-EM), revealing in situ atomic models of three minor capsid proteins (IIIa, VIII, and IX), extensions of the (penton base and hexon) major capsid proteins, and interactions within three protein-protein networks. One network is mediated by protein IIIa at the vertices, within group-of-six (GOS) tiles--a penton base and its five surrounding hexons. Another is mediated by ropes (protein IX) that lash hexons together to form group-of-nine (GON) tiles and bind GONs to GONs. The third, mediated by IIIa and VIII, binds each GOS to five surrounding GONs. Optimization of adenovirus for cancer and gene therapy could target these networks.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095-7364, USA.
authors.forename: Hongrong
authors.initials: H
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Sok Boon S
authors.initials: SB
authors.lastname: Koh
authors.forename: Ivo
authors.initials: I
authors.lastname: Atanasov
authors.forename: Stan
authors.initials: S
authors.lastname: Schein
authors.forename: Lily
authors.initials: L
authors.lastname: Wu
authors.forename: Z Hong
authors.initials: ZH
authors.lastname: Zhou
mesh_terms: D000260:Adenoviruses, Human / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D002213:Capsid / Q000737:chemistry / Q000648:ultrastructure; D036022:Capsid Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D020285:Cryoelectron Microscopy; D016679:Genome, Viral; D007091:Image Processing, Computer-Assisted; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D014771:Virion / Q000737:chemistry / Q000648:ultrastructure
chemical_list: D036022:Capsid Proteins; C018315:hexon capsid protein, Adenovirus; C043322:penton protein, adenovirus
references.citation: J Bacteriol. 1965 Jul;90(1):254-61
references.pmid: 16562026
references.citation: J Chromatogr B Biomed Sci Appl. 1999 Sep 24;732(2):411-23
references.pmid: 10517364
references.citation: J Gen Virol. 2009 Jan;90(Pt 1):1-20
references.pmid: 19088268
references.citation: J Gen Virol. 1998 Jul;79 ( Pt 7):1671-5
references.pmid: 9680130
references.citation: J Mol Biol. 2003 Oct 31;333(4):721-45
references.pmid: 14568533
references.citation: Nature. 2006 May 11;441(7090):239-43
references.pmid: 16625206
references.citation: Cell. 2008 Feb 8;132(3):397-409
references.pmid: 18267072
references.citation: J Virol. 2005 Feb;79(4):1992-2000
references.pmid: 15681401
references.citation: Cell. 1991 Oct 4;67(1):145-54
references.pmid: 1913814
references.citation: Nature. 2006 Feb 2;439(7076):612-6
references.pmid: 16452981
references.citation: Mol Ther. 2004 Oct;10(4):616-29
references.pmid: 15451446
references.citation: J Virol. 2003 Sep;77(17):9553-66
references.pmid: 12915569
references.citation: Biochim Biophys Acta. 2003 May 30;1648(1-2):1-11
references.pmid: 12758141
references.citation: J Virol. 1981 Sep;39(3):977-80
references.pmid: 7288921
references.citation: J Mol Biol. 2009 Sep 18;392(2):547-57
references.pmid: 19563809
references.citation: J Virol. 2009 Feb;83(4):2025-8
references.pmid: 19036812
references.citation: Virology. 1972 Sep;49(3):745-57
references.pmid: 5072634
references.citation: J Mol Biol. 1972 Jul 14;68(1):181-4
references.pmid: 5050362
references.citation: Nature. 1999 Oct 28;401(6756):935-8
references.pmid: 10553913
references.citation: J Virol. 2007 Apr;81(7):3640-4
references.pmid: 17215290
references.citation: Virology. 1980 Feb;101(1):144-56
references.pmid: 7355575
references.citation: J Virol. 2006 Dec;80(24):12049-59
references.pmid: 17005667
references.citation: J Virol. 2006 Dec;80(23):11881-6
references.pmid: 16987967
references.citation: Mol Cell. 2005 Jan 7;17(1):121-35
references.pmid: 15629723
references.citation: EMBO J. 2005 May 4;24(9):1645-54
references.pmid: 15861131
references.citation: Science. 1986 May 30;232(4754):1148-51
references.pmid: 3704642
references.citation: J Virol. 2009 Jan;83(2):1135-9
references.pmid: 19004948
references.citation: EMBO J. 1993 Jul;12(7):2589-99
references.pmid: 8334984
references.citation: Gene Ther. 2004 Mar;11(6):504-11
references.pmid: 14999222
references.citation: J Mol Biol. 1985 Sep 5;185(1):125-43
references.pmid: 4046035
references.citation: Nat Nanotechnol. 2010 Jan;5(1):48-53
references.pmid: 19935648
references.citation: Nature. 2004 Nov 4;432(7013):68-74
references.pmid: 15525981
references.citation: Curr Gene Ther. 2004 Sep;4(3):337-46
references.pmid: 15384947
references.citation: J Struct Biol. 2002 Mar;137(3):292-304
references.pmid: 12096897
references.citation: Nature. 2004 Nov 4;432(7013):122-5
references.pmid: 15525993
references.citation: J Virol. 2009 Aug;83(15):7375-83
references.pmid: 19458007
references.citation: Virology. 1975 Sep;67(1):197-208
references.pmid: 808902
references.citation: J Cell Biochem. 2005 Sep 1;96(1):25-35
references.pmid: 15988756
references.citation: J Mol Biol. 1968 Nov 14;37(3):379-86
references.pmid: 5719215