title: Crystal structure of human adenovirus at 3.5 A resolution.
abstract: Rational development of adenovirus vectors for therapeutic gene transfer is hampered by the lack of accurate structural information. Here, we report the x-ray structure at 3.5 angstrom resolution of the 150-megadalton adenovirus capsid containing nearly 1 million amino acids. We describe interactions between the major capsid protein (hexon) and several accessory molecules that stabilize the capsid. The virus structure also reveals an altered association between the penton base and the trimeric fiber protein, perhaps reflecting an early event in cell entry. The high-resolution structure provides a substantial advance toward understanding the assembly and cell entry mechanisms of a large double-stranded DNA virus and provides new opportunities for improving adenovirus-mediated gene transfer.
authors.affiliation: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. reddyv@scripps.edu
authors.forename: Vijay S
authors.initials: VS
authors.lastname: Reddy
authors.forename: S Kundhavai
authors.initials: SK
authors.lastname: Natchiar
authors.forename: Phoebe L
authors.initials: PL
authors.lastname: Stewart
authors.forename: Glen R
authors.initials: GR
authors.lastname: Nemerow
mesh_terms: D000260:Adenoviruses, Human / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure*; D002213:Capsid / Q000737:chemistry* / Q000648:ultrastructure*; D036022:Capsid Proteins / Q000737:chemistry* / Q000648:ultrastructure; D018360:Crystallography, X-Ray; D005822:Genetic Vectors; D006860:Hydrogen Bonding; D008958:Models, Molecular; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry; D053586:Virus Internalization
chemical_list: D036022:Capsid Proteins; D021122:Protein Subunits; C018315:hexon capsid protein, Adenovirus; C043322:penton protein, adenovirus
references.citation: J Virol. 2006 Dec;80(24):12049-59
references.pmid: 17005667
references.citation: J Gene Med. 2004 Jun;6(6):597-602
references.pmid: 15170730
references.citation: J Virol. 2000 Nov;74(22):10274-86
references.pmid: 11044071
references.citation: EMBO J. 1993 Jul;12(7):2589-99
references.pmid: 8334984
references.citation: Cornea. 2006 Feb;25(2):199-202
references.pmid: 16371782
references.citation: J Virol. 2005 Feb;79(4):1992-2000
references.pmid: 15681401
references.citation: J Virol. 2009 Aug;83(15):7375-83
references.pmid: 19458007
references.citation: Proc Soc Exp Biol Med. 1954 Jan;85(1):183-8
references.pmid: 13134329
references.citation: J Mol Biol. 2005 Jun 10;349(3):526-37
references.pmid: 15890367
references.citation: Rev Med Virol. 2008 Nov-Dec;18(6):357-74
references.pmid: 18655013
references.citation: J Infect Dis. 2007 Nov 15;196(10):1465-73
references.pmid: 18008225
references.citation: J Am Coll Cardiol. 2007 Sep 11;50(11):1038-46
references.pmid: 17825712
references.citation: Nature. 1999 Oct 28;401(6756):935-8
references.pmid: 10553913
references.citation: Virology. 2010 Jun 20;402(1):209-14
references.pmid: 20394956
references.citation: Pediatr Transplant. 2006 Feb;10(1):17-25
references.pmid: 16499582
references.citation: J Virol. 1985 Nov;56(2):439-48
references.pmid: 4057357
references.citation: Curr Gene Ther. 2007 Jun;7(3):189-204
references.pmid: 17584037
references.citation: Mol Cell. 2005 Jan 7;17(1):121-35
references.pmid: 15629723
references.citation: Invest Ophthalmol Vis Sci. 1996 Dec;37(13):2774-8
references.pmid: 8977495
references.citation: EMBO J. 2005 May 4;24(9):1645-54
references.pmid: 15861131
references.citation: J Virol. 1999 Feb;73(2):1601-8
references.pmid: 9882366
references.citation: Hum Gene Ther. 2003 May 20;14(8):777-87
references.pmid: 12804140
references.citation: Mol Ther. 2000 Jan;1(1):18-30
references.pmid: 10933908
references.citation: J Mol Biol. 2006 Feb 17;356(2):510-20
references.pmid: 16375921