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Figure 2.
(a) Topological and conformational dynamics of R^21
activation. Crystal structures of ^iR^21 (left) and ^aR^21
(right) are represented in cartoon format, with  -helix
in cyan,  -strand
in magenta and coil in salmon; the SAR domain is shown in orange
and is depicted as a membrane-spanning helix in ^iR^21. The
catalytic triads are represented in stick-and-ball form, with
disulfide linkages in yellow stick. (b) Alignment of the
catalytic loop regions of ^iR^21 (green) and ^aR^21 (salmon).
Except for Glu35, which shows a 10-Å C displacement
(dashed line), most of the catalytic loop (Ser38–Thr67) of
^aR^21 can be superimposed on the same region of ^iR^21 (r.m.s.
difference = 0.4 Å for 209 atoms). (c) Alignment of the
C-terminal domains of ^iR^21 and ^aR^21, colored as in b.
Beginning at Glu96, the backbone r.m.s. difference between the
two structures is 4.0 Å. Helix 8
in ^iR^21 tilts 30°, turns and unwinds compared to ^aR^21,
thereby turning Arg152 away from Glu35. (d) Polarity switching
at the interface for the SAR domain. The calculated
electrostatic surface (positive = blue; negative = red)
contacting the helices of the extracted SAR domain for ^aR^21 is
shown at right; the corresponding surface is ^iR^21 is shown at
left, with the SAR helices superimposed as an orange backbone
ribbon trace.
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