A Generalized Allosteric Mechanism for cis-Regulated Cyclic Nucleotide Binding Domains
Figure 8
General allosteric mechanism for different CNB domains (RIα∶A case).
(A) Major interactions between cAMP, the PBC (red) and the β2,3-loop (black) in cAMP-bound state. Red circles represent residues forming polar bonds (red arrows); yellow circles show residues making hydrophobic contacts (green arrows). The most important bond between cAMP and R209 is shown by a double red arrow. Residues and structure elements changing their positions upon cAMP binding are shaded grey. (B) cAMP-free configuration. R209 becomes much less restricted. (C) General diagram of major interactions in the CNB domain. The PBC controls cAMP, the 310-loop controls R209, and their interaction provides correct orientation of the hinge region and the N3A motif, which form a protein-protein interface.