Bimodal kinetics of CNB domains monitor PDE8-mediated cAMP release from RIα. Mass spectra of peptides CNB:A (residues 203–222, left column) and CNB:B (residues 329–346, right column), for RIαAB and PDE8AC-RIαAB at different deuterium labeling (tDex) times are shown. Centroids are indicated by red triangles. The bimodal kinetics represent at least two populations—a lower-exchanging population of ligand-bound RIαAB, highlighted in blue, and a higher-exchanging population of ligand-free RIαAB, highlighted in orange. To see this figure in color, go online.