Crystal structure of human adenovirus at 3.5 A resolution.
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.
Reddy
Vijay S
VS
The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. reddyv@scripps.edu
Natchiar
S Kundhavai
SK
Stewart
Phoebe L
PL
Nemerow
Glen R
GR
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
D036022:Capsid Proteins; D021122:Protein Subunits; C018315:hexon capsid protein, Adenovirus; C043322:penton protein, adenovirus
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