Adenovirus hexon protein

Carlisle RC, Bettinger T, Ogris M, Hale S, Mautner V, Seymour LW (2001) Adenovirus hexon protein enhances nuclear delivery and increases transgene expression of polyethy-lenimine/plasmid DNA vectors. Mol Ther 4 473 183... 

Crawford-MikszaL, Schnurr DP. Analysis of 15 adenovirus hexon proteins reveals the location and structure of seven hypervaiiable regions containing serotype-specific residues. J Virol 1996 70 1836-1844. 

Perhaps the most spectacular homology seen to date is the similarity between the hexon protein of a mammalian virus, adenovirus, and the P3 coat protein of a bacteriophage PRDl, both containing two jelly-roll domains (Athappilly et al, 1994 Benson et al, 1999). This only goes to show that as our understanding of other viral proteins expands, so will the homologies that will likely become apparent. 

The adenovirus capsid is an icosahedral capsid that can be described as pseudo-T=25. The 12 pentameric vertices are each composed of 5 molecules of the penton bases, carrying a trimeric fiber. The 20 faces are composed of the 4 molecules of hexon protein, which itself is a trimer of the 967-residue-long polypeptide II. The crystal structure of the hexon has been solved and it reveals that the trimeric subunits are intimately intertwined, thus accounting for their observed stability. The capsid also... 

Blanche F, Cameron B, Somarriba S, et al. (2001). Stabilization of recombinant adenovirus Site-directed mutagenesis of key asparagine residues in the hexon protein. Anal. Biochem. 297 1-9. 

Ostapchuk P, Hearing P. Pseudopackaging of adenovirus type 5 genomes into capsids containing the hexon proteins of adenovirus serotypes B, D, or E. J Virol 2001 75 45-51. 

Larger icosahedral viruses that have been structurally well characterized do not obey the simple quasi-equivalence rule. For example, adenovirus capsids, for which T = 25, are built of 240 hexons (six-coordinated units) that are trimers of the major structural protein, and the 12 pentons consist of a different protein (Burnett 1984). Polyomavirus capsids, for which T = 7, are built of a single major structural protein,... 

Burnett, R. M. 1984 Structural investigations of hexon, the major coat protein of adenovirus. In Biological macromolecules and assemblies (Volume 1 Virus structures) (ed. F. A. Jurnak A. McPherson), pp. 377-385. New York John Wiley Sons. 

Fig. 4. Adenovirus and bacteriophage PRDl. Top On the left, a density isosurface representation of adenovirus at 25-A resolution is shown. The 5-fold axis, occupied by the protein penton, is marked with a pentagon. A trimer of hexon is marked with a triangle close by arrays of hexon extend outward in all directions from the pentagonal vertex, forming the flat faces of the virus. On the right, a close-up of the 5-fold axis is shown (top) and below that a close-up of the hexon trimer with it crystal structure fitted (Athappilly et at, 1994 Stewart et al, 1991). Bottom The Susl mutant of PRDl is shown...

Combining these two approaches, by determining the crystal structure of individual subcomponents and fitting these into the lower resolution maps of intact particles, may offer the best current hope for obtaining high-resolution information about virion structure. An example of this is provided by adenovirus, where the crystal structure of the hexon, formed by three copies of the 100-kDa major structural protein, has been fitted into a low-resolution capsid structure determined by electron cryomicro-scopy to provide a clearer picture of capsid organization and information about the locations of minor capsid proteins (Stewart et al, 1993). A similar strategy has been used to fit the crystal structure of a portion of the HSV-1 major capsid protein (VPS) into an intermediate-resolution map of the capsid (B. Bowman, personal communication). 

FIGURE 10.4 Several consecutive sections of the electron density of the hexon capsid protein from adenovirus are stacked and displayed on a light box. Here the continuity of the polypeptide begins to emerge. Some recognizable features such as the two a helices marked by arrows are also evident to... 

Figure 10.1-3. Schematic structure of an adenovirus particle. Major capsid (hexon, penton, fiber) and core (pV, pVII, Mu) proteins are shown. Abbreviation ITR—inverted terminal repeat TP—terminal protein. (Adapted from Ref. 27.)...

Adenoviruses consist of a large double-stranded DNA genome (about 36 kilobase pairs long) packaged within a nonenveloped icosahedral capsid that is primarily composed of three virus-encoded proteins (hexon, pen ton base, and fiber proteins) [39]. The fiber proteins protrude fi om the surface of the virus and mediate its attachment to target cells via a high affinity interaction with the cellular receptor CAR (coxsackievirus and adenovirus receptor) [40]. The virus is then internahzed into endosomal vesicles via specific interactions between the penton base proteins and ofy integrins [41]. Adenoviruses escape these vesicles by an acid-induced endosomolytic activity and are transported to the nucleus, into which they enter via pores in the nuclear membrane [42]. 

Athappilly FK, Murali R, Rux JJ, Cai Z, Burnett RM. The refined crystal structure of hexon, the major coat protein of adenovirus type 2, at 209 A resolution. J... 

Roy S, Shirley PS, McClelland A, Kaleko M. Circumvention of immunity to the adenovirus major coat protein hexon. J Virol 1998 72 6875 879. 

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