Ca 2 - Myristoyl Switch in the Neuronal Calcium Sensor

Recoverin is an EF-hand Ca -binding protein that is suggested to control the activity of the G-protein-coupled receptor kinase GRK-1 or rhodopsin kinase in a Ca -dependent manner. It undergoes a Ca -myristoyl switch when Ca binds to EF-hand 2 and 3. We investigated the mechanism of this switch by the use of point mutations in EF-hand 2 (E85Q) and 3 (E121Q) that impair their Ca binding. EF-hand 2 and 3 display different properties and serve different functions. Binding of Ca to recoverin is a sequential process, wherein EFhand 3 is occupied first followed by the filling of EFhand 2. After EF-hand 3 bound Ca , the subsequent filling of EF-hand 2 triggers the exposition of the myristoyl group and in turn binding of recoverin to membranes. In addition, EF-hand 2 controls the mean residence time of recoverin at membranes by decreasing the dissociation rate of recoverin from membranes by 10fold. We discuss this mechanism as one critical step for inhibition of rhodopsin kinase by recoverin.