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Figure 3.
Figure 3. X-ray structure of the PB2 C-terminal domain complexed
with importin  5.
(a) Ribbon diagram showing DPDE (red) bound to human importin
 5
(blue), comprising ten armadillo repeats. The C-terminal helix
of the importin is unpacked and mediates domain-swap dimer
formation in the crystal. The bipartite NLS at the C terminus of
DPDE binds classically within the superhelical groove of
importin 5.
Basic residues Arg737, Lys738 and Arg739 from the minor site
(purple) interact with the C-terminal armadillo repeats; Lys752,
Arg753 and Arg755 from the major site (gold) interact with the
N-terminal armadillo repeats. Lys736 does not interact with
importin 5
but makes intramolecular hydrogen bonds in DPDE, perhaps
preventing further unfolding of the C terminus. Lys718 makes
three hydrogen bonds with importin 5.
(b) Comparison of the PB2 domain structure in complexed (red)
and free solution state (cyan) demonstrates unfolding of
residues 736–759 (purple) upon binding to importin 5.
Residue Asp701, important in host specificity and virulence,
forms a salt bridge with Arg753 of the major NLS motif and
tethers the C terminus to the core of the domain in the unbound
state. Residues Arg702 and Ser714 are also implicated in
interspecies transmission. Note different orientations of the
N-terminal helix of DPDE in the two structures.
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