|
Figure 2.
Predicted structural determinants of Gα selectivity by RGS2.
(A) RGS1 (gray-blue) bound to Gα[i1] (α1 helix in light red;
switch I in orange) is presented to highlight the Gα switch-I
interaction interface (PDB ID 2GTP). Asp-172 of RGS1 is within
hydrogen-bonding distance of the backbone amine of Thr-182 in
Gα[i1] and additionally stabilized by the terminal amines of
the highly conserved Arg-176 in the RGS1 αVII helix. Ser-95 is
placed within close proximity (≤4.0 Å) of three Gα[i1]
residues (Thr-182, Gly-183, and Lys-210). (B) Residues 170–190
of RGS2 (PDB ID 2AF0) were superimposed on residues 159–179 of
RGS1 from the RGS1/Gα[i1] complex (PDB ID 2GTP) with an
r.m.s.d. of 0.5 Å. RGS1 is not shown, RGS2 is presented in
green, and Gα[i1] is rendered in light red (α1 helix) and
orange (switch I). Asparagine at position 184 in RGS2 (normally
an aspartate in R4 subfamily members) does not allow for the
hydrogen bond to the peptide bond amine of Thr-182 in Gα[i1];
however, Asn-184 can potentially form a hydrogen bond with the
backbone carbonyl of Lys-180. The increased atomic radius of
Cys-106 in RGS2 (versus serine in RGS1) may cause steric
hindrance with the switch-I backbone and the side-chain of
Lys-210.
|
