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protein, a protein with an EF-hand calmoduline motif; and amino acids
718-897 displayed homology to the tumor suppressor bin1
(amphiphysin II), which belongs to a family of adapter proteins that
have been implicated in a variety of different cellular processes, includ-
ing endocytosis, actin cytoskeletal organization, transcription, and stress
responses. 56 Although the sequence corresponding to the HAstV pro-
tease showed structural relationship to the protease motif of the heat
shock protein DegP (Htra) of Escherichia coli , the NCBI conserved
domain search identified homology to the Equine arterivirus serine
endopeptidase S32 (pfam 05579). Although not contained within the
significant alignment, both proteases contain a C-terminal extension
domain that may play a role in mediating protein-protein interactions,
which may be a novel way of regulating its proteolytic activity. 57,58
Using similar approaches, an extensive proteomic computational
analysis was performed for HAstV-4 nsP1a C-terminal product. 47 This
analysis indicated that the proportion of residues that were not
assigned to a particular secondary structure was higher within this
region of nsP1a than in other regions of the genome, revealing the
high degree of structural flexibility that this region may have. Accord-
ingly, analysis of genetic variability revealed that this region was the
most variable region of the whole nonstructural coding region, show-
ing a high degree of tolerance to insertions and deletions. The authors
also suggested a higher occurrence of post-translational modifica-
tion motifs, such as phosphorylation and O-glycosylation. Although
sequence homology searches only displayed proteins with a moderate
degree of similarity, the most significant results involved nonstructural
proteins from single-stranded RNA viral families involved in the for-
mation of the RNA replicase complexes and/or in the regulation of
both viral and cellular transcription processes, and at the superfamily
level, the protein was assigned to the “winged-helix” DNA-binding
domain superfamily (SSF46785).
HAstV Replication Cycle
Replication of genomes of all well-characterized positive-strand RNA
viruses — including plant, animal, and insect viruses — occurs in large
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