FIGURE 11.

Schematic diagram showing the ways in which CPM interacts with the B1R to facilitate kinin signaling. A model of GPI-anchored CPM and its potential membrane orientation based on its crystal structure and interactions with the B1R are shown. Based on our studies, CPM enhances B1R signaling in three ways; 1) basal binding of CPM allosterically enhances B1R affinity for its des-Arg-kinin agonist, 2) kinin substrate (i.e. BK or KD) binding to the CPM active site causes a conformational change in CPM that is transmitted via protein-protein interaction to the B1R, resulting in G protein coupling and activation of calcium, nitric oxide (NO), or ERK signaling, and 3) cleavage of the C-terminal Arg of KD (or BK) by CPM generates B1R agonist (e.g. DAKD) that can further activate the associated receptor or additional B1Rs.