Biology Reference
In-Depth Information
Fig. 2.
Ribbon diagram of Ebola virus VP40. Two amino- and carboxy-
terminal domains can be seen in red and green, respectively. Courtesy of
Dessen
et al
., 2000.
from Ebola virus has been resolved to 2.0 Å
11
and has revealed that
VP40 consists of two structurally homologous domains that comprise
six antiparallel
-sheets (Fig. 2). The
amino- and carboxy-terminal domains are oriented at an angle of 60
β
-strands arranged in two
β
,
and are connected by a large flexible loop.
11
VP40 binds strongly to
lipid membranes. This binding is resistant to high salt concentrations
and appears to be mediated by the C-terminal domain,
6,8
which con-
tains large hydrophobic patches.
11
The current model predicts that VP40 exists in the cytoplasm as
a monomer that is stabilized by interactions between its amino- and
carboxy-terminal domains. Destabilization of these interactions liber-
ates the amino-terminal domain to interact with other VP40 mole-
cules and thus form oligomers. This destabilization can be achieved
experimentally by a carboxy-terminal truncation of seven amino acids
that induces spontaneous hexamerization and the formation of ring-
like structures, as demonstrated by chemical cross-linking and elec-
tron microscopy,
12
or by membrane association.
12
After the liberation
of the amino-terminal domain, VP40 is thought to adopt dimeric and
octameric forms; the dimeric VP40 appears to be the building block
for both hexameric and octameric structures.
13
The carboxy-terminal
°
