Biology Reference
In-Depth Information
recognition and allows us to assign additional specific contacts, in par-
ticular those involving the (
2,6)-linked, branching sialic acid. The
structure of the unliganded VP1-pentamer, determined independ-
ently, shows that the oligosaccharide fits into a preformed groove and
induces no measurable structural rearrangements. A comparison with
assembled VP1 in the virus capsid reveals a rearrangemnt of residues
32-45 at the base of the pentamer. This segment may help prevent
the formation of incorrectly assembled particles by reducing the like-
lihood that the C-terminal arm will fold back into its pentamer of
origin. Biochemical assay improved the notion for polyomavirus bind-
ing to oligosaccharide receptor recognition. Binding and flotation
assays showed that addition of gangliosides to the phospholipids vesi-
cles allowed specific binding of the respective viruses. Specific gan-
gliosides can serve as plasma membrane receptors, GD1a and GT1b
for polyomavirus, GM1 for SV40,
40
and GD1b and GT1b for BK.
41
After host cell surface binding through cell surface proteins and
gangliosides, it has been suggested that the local structure of virion
changes during endocytosis
42
and this change is involved with its cal-
cium binding sites.
43,44
Several lines of evidence have suggested that
this inter VP1-pentamer interaction is strengthened by calcium ion
chelation and disulfide bonding. Structural refinement on SV40, in
which divalent calcium ions were replaced with trivalent gadolinium
ions, has identified two probable sites, termed site-1 and site-2, of
calcium ion coordination per VP1 monomer on the capsid (Fig. 5).
Site-1 consists of the Glu 216 side chain and Ser 213 of one VP1
monomer, the Glu 46 and Glu 48 side chains of a second VP1 monomer
from the same pentamer, and the Glu 330 side chain (C-terminal
arm) of a third VP1 monomer from a neighboring pentamer. Site-2
consists of the Glu 157, Glu 160, and Glu 216 side chains and Lys
214 carbonyl oxygen of the first VP1 monomer and the Asp 345 side
chain (C-terminal arm) of the third monomer. Each pair of calcium
ions is expected to tie together two different VP1 pentamers by inter-
acting with mostly acidic amino acid residues contributed by three
VP1 chains. The point mutant E330K VLPs of SV40, site-1 calcium
mutant, turned out to be defective in adsorbing to cells.
43
Conceivably,
the salt bridges in place of calcium ion at site-1 could have prevented
α
