ABSTRACT
The three-dimensional structure of soluble recombinant integrin αvβ5 bound to human adenovirus types 2 and 12 (Ad2 and -12) has been determined at ∼21-Å resolution by cryoelectron microscopy (cryo-EM). The αvβ5 integrin is known to promote Ad cell entry. Cryo-EM has shown that the integrin-binding RGD (Arg-Gly-Asp) protrusion of the Ad2 penton base protein is highly mobile (P. L. Stewart, C. Y. Chiu, S. Huang, T. Muir, Y. Zhao, B. Chait, P. Mathias, and G. R. Nemerow, EMBO J. 16:1189–1198, 1997). Sequence analysis indicated that the Ad12 RGD surface loop is shorter than that of Ad2 and probably less flexible, hence more suitable for structural characterization of the Ad-integrin complex. The cryo-EM structures of the two virus-receptor complexes revealed a ring of integrin density above the penton base of each virus serotype. As expected, the integrin density in the Ad2 complex was diffuse while that in the Ad12 complex was better defined. The integrin consists of two discrete subdomains, a globular domain with an RGD-binding cleft ∼20 Å in diameter and a distal domain with extended, flexible tails. Kinetic analysis of Ad2 interactions with αvβ5 indicated ∼4.2 integrin molecules bound per penton base at close to saturation. These results suggest that the precise spatial arrangement of five RGD protrusions on the penton base promotes integrin clustering and the signaling events required for virus internalization.
Genomic characterization of a novel human adenovirus type 31 recombinant in the hexon gene
