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capsid biology. This approach has recently been used by two different
research groups, leading to similar conclusions. 27,35 Consistently, all
significant matches for VP34 sequence from different HAstV serotypes
and other animal astroviruses correspond to coat proteins from sim-
ple, icosahedrally symmetric viruses with jelly-roll
-barrel subunits,
such as Theiler's murine encephalomyelitis virus, bean pod mottle
virus, carnation mottle virus, and tomato bushy stunt virus. Structural
alignments of predicted structural homology comparisons between a
fragment of VP34 sequence and coat proteins from these viruses are
shown in Fig. 3. Interestingly, the putative RNA-binding domain
present at the N-terminus of VP34 was never included in positive
alignments, confirming a different biological function for these two
domains of the VP34 protein.
The evaluation of protein-folding prediction for the variable domain
(amino acid 416 to the end of ORF2) showed significant structural
homology to virus-related proteins and receptors, as well as to some
non-viral receptor-ligand interactions. 35 These results support the idea
that this capsid protein domain is responsible for the receptor-interac-
tion process, which dictates cell tropism and may vary enormously
between different astrovirus strains. 35 Of interest, most significant align-
ments did not include the C-terminal region of ORF2, suggesting that
this sequence would not be included in the infectious particle, as some
of the proposed models of morphogenesis suggest. 8
These prediction results would indicate that capsid proteins
from all astroviruses fold in a manner similar to that of well-studied
ssRNA icosahedral viruses with T
β
=
3 symmetry, and that the pre-
dicted
-barrel domain found in VP34 protein could be the building
block for capsid assembly. One common feature of ssRNA viruses that
show T
β
3 symmetry is that their capsids are made of a single struc-
tural building block. Assuming that 180 copies of the VP34 protein
are required to give a particle of 33 nm with T
=
3 symmetry and that
the spikes are formed by VP26 and VP29 proteins would be consistent
with the structural prediction that suggests that VP34 is a structural
homolog to known icosahedral coat proteins and that the variable
domain (VP26/VP29) is involved in receptor binding.
=
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