|
Figure 5.
Fig. 5. The clamping of the helical hairpin. (a) View of
RasGRF1 showing the helical hairpin (red), flap1, and flap2
(both gray). (b) A cutaway view through the catalytic Ras
binding site of RasGRF1. A tight interface between flap1 and the
helical hairpin of RasGRF1 is formed by bulky, hydrophobic
residues (Phe-1052, Phe-1051, and Tyr-1048 in flap1, Ile-1214,
and Ile-1210 in the helical hairpin). A salt-bridge network and
hydrophobic interactions connect the helical hairpin with flap2
(Met-1181 and Phe-1188 bury Asp-1185 in the helical hairpin,
bridging to Arg-1160 and Arg-1165 in flap2). (c) In the active
conformation of Sos, the helical hairpin (dark blue) is similar
in position to that of RasGRF1, but the interface with flap1 is
not well packed (Val-805, Leu-804, and Pro-801 in flap1, Thr-964
and Val-968 in the helical hairpin). (d) In the absence of
allosteric Ras binding, the helical hairpin of uncomplexed Sos
(light blue) collapses inward to interact more closely with
flap1. Neither active nor inactive Sos helical hairpins form
close interactions with flap2 (Lys-939, Ile-932, and Asn-936 in
the helical hairpin do not form contacts with His-911 and
Leu-916 in flap2).
|
