Figure 4.
Fig. 4. Structural identification of an ancient permissive
substitution. (A) Comparison of the structures of AncCR (blue)
and AncGR2 (yellow). Y27R generates a novel cation- interaction in
AncGR2 (dotted cyan line), replacing the weaker ancestral
hydrogen bond (dotted red) and imparting additional stability to
helix 3. (B) Y27R is permissive for the substitutions that
confer GR function. Reporter gene activation by AncGR1 + XYZ
(upper right) is abolished when Y27R is reversed (lower right).
(Left) Y27R has negligible effect in the AncCR background (or in
AncGR1, fig. S9). Green, orange, and purple lines show
aldosterone, DOC, and cortisol responses, respectively. Green
arrows, likely pathway through functional intermediates.
The above figure is reprinted
by permission from the AAAs:
Science
(2007,
317,
1544-1548)
copyright 2007.
interaction in
AncGR2 (dotted cyan line), replacing the weaker ancestral
hydrogen bond (dotted red) and imparting additional stability to
helix 3. (B) Y27R is permissive for the substitutions that
confer GR function. Reporter gene activation by AncGR1 + XYZ
(upper right) is abolished when Y27R is reversed (lower right).
(Left) Y27R has negligible effect in the AncCR background (or in
AncGR1, fig. S9). Green, orange, and purple lines show
aldosterone, DOC, and cortisol responses, respectively. Green
arrows, likely pathway through functional intermediates.