Biology Reference
In-Depth Information
assembly. In addition, it can modulate metabolism in infected cells via
interactions with several cellular proteins, e.g. with Daxx- and
SUMO-1-pathway members. In this chapter we review the current
knowledge on hantaviral N protein structure and functions. We also
present new data on a 3D-structure of the hantaviral N-ptotein trimer
and discuss its possible role in the viral replication cycle. Finally, we
describe the structure of the N protein oligomers and polymers.
General Features of the N Protein
The N protein of hantaviruses contains 429 to 433 aa residues. The
protein sequence is well conserved within a given hantavirus type and,
to a lesser extent, among all hantaviruses. Analysis of the sequence
conservation reveals three conserved regions separated by two more
variable regions spanning aa 50-80 and 230-310.
8
The central con-
served region contains a cluster of positively charged residues that
overlaps with a putative RNA-binding domain.
9
Formation of RNPs, which are functional templates for transcrip-
tion and replication of the viral genome, depends on interactions of
the N protein with several partners: vRNA, other N protein molecules,
and, perhaps, the L protein. Terminal panhandle-forming regions of
the vRNA molecules seem to possess a unique binding region for
the N protein.
10-12
The corresponding sequences of the cRNAs are
recognized with lower affinity. Recently solved 3D structures of the
N proteins of lyssa- and rhabdoviruses
13,14
implied a conformational
change of the nucleocapsid protein molecule, which is essential for
RNA encapsidation. Most probably, this conformational change
results from interaction not only between the N protein and viral
RNA but also between two (or more) molecules of the N protein: to-
be-recruited RNA-binder and neighboring molecule(s) that have been
already engaged with RNA and have adopted a new conformation.
This model is in agreement with experimental data on
in vitro
binding
of recombinant GST-N-trimer to the viral RNA panhandle.
12
Binding
of the N-trimer to the panhandle might have important conse-
quences. According to the model suggested by Mir and Panganiban,
15
the trimer can work as an RNA chaperone causing dissociation of
