Polyomavirus structure

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,... 

Polyoma- and papillomaviruses share a common capsid structure that is assembled from 72 pentameric capsomeres arranged on a T = 7 icosahedral lattice. Assembly studies of polyomaviruses were first initiated by expression of the major capsid protein of mouse polyomavirus, VPl, in... 

The structure of a small VLP of human papillomavirus 16 was solved by X-ray crystallography (Chen et al, 2000). The particles were first assembled in vitro from pentameric capsomers generated in E. coli. To obtain highly diffracting crystals, the N terminus (10 amino acid residues) had to be removed from the LI protein. While this did not interfere with capsomer formation, the protein assembled into T = 1 particles containing 12 capsomers instead of the usual 72 capsomers. Thus the term small VLP. The crystal structure of the small VLP at 3.5-A resolution showed that the LI protein closely resembles the VPl protein of polyomaviruses and that surface loops contain the sites of sequence variation among different HPV types. These loops also represent dominant, neutralizing epitopes. The crystal structure now serves as a tool for current and future vaccine development. 

The family Polyomaviridae includes both polyomavirus and simian virus 40 (SV40), whose structures are both known at atomic resolution (Liddington et at, 1991 Stehle et al., 1994, 1996). These viruses had been grouped within the Papovavirus family with other tumor-inducing papillomaviruses that have been studied by electron microscopy, but not at atomic resolution (Baker et al., 1991 Trus et al, 1997). The families have now been recategorized separately (van Regenmortel et al, 2000). They share similar genetic structure, but little sequence similarity between capsid proteins, and show some differences in overall dimensions (Baker et al, 1991). 

An explanation came with the atomic structures (Garcia and Liddington, 1997 Liddington et al, 1991 Stehle et al, 1994, 1996). It extended our ideas of quasi-equivalence that previously had been implicidy limited to considering the interactions between relatively rigid globular domains. In the polyomaviruses the contacts between capsomers are not barrel to... 

Papillomavirus is difficult to produce in amounts suitable for structural studies, but the particles, like polyoma and SV40, appear to be built up of 72 pentamers. Recombinant expression of the main capsid protein, LI, in bacteria leads to capsids with 12 pentamers, and it has been possible to study these by crystallography (Chen et al, 2000). The C-terminal segment of the chain that is exchanged between pentamers in polyomavirus is in the papillomavirus recombinant capsids forming a projection, but the chain returns to the jellyroll from where it emanates. In the native T=7 particles, this region is probably exchanged between pentamers like in polyomavirus. 

Garcia, L. R., and Liddington, R. C. (1997). Structural Biology of Polyomaviruses. Oxford University Press, New York. 

Structural information is available for the J domains of E. coli DnaJ, human DjBl/Hdj-1, and polyomavirus T-antigen (Szyperski et al., 1994 Pellecchia et al., 1996 Qian et al., 1996 Beijanskii et al., 2000 see Section III.B.2.b), the Zn-binding domain of E. coli DnaJ (residues 121— 209 Martinez-Yamout et al., 2000), and the C-terminal domain of yeast Sisl (residues 171-352) which has homology to the C-terminal domain... 

Stehle T, Harrison SC (1997) High-resolution structure of a polyomavirus VP 1-oligosaccharide complex implications for assembly and receptor binding. EMBO J 16 5139-5148... 

Stehle T, Yan Y, Benjamin TL, Harrison SC (1994) Structure of murine polyomavirus complexed with an oligosaccharide receptor fragment Nature 369 160-163... 

Stehle T, Harrison SC (1996) Crystal structures of murine polyomavirus in complex with straight-chain and branched-chain sialyloligosaccharide receptor fragments. Structure 4 183-194... 

Neu U, Maginnis MS, Palma AS, et al. Structure-function analysis of the human JC polyomavirus establishes the LSTc pentasaccharide as a functional receptor motif. Cell Host Microbe. 2010 8(4) 309-319. 

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