Figure 8. Target-myristoyl switch in CHP3.

N-terminal myristoylation of CHP3 by NMT1 increases the local flexibility in the N-lobe, as it accelerated its tryptic cleavage. The myristoyl moiety most likely binds weakly or transiently to the target-binding pocket in both Ca²⁺- and Mg²⁺-bound states, as myristoylation reduced twofold the affinity of CHP3 to CBD. CBD binding causes displacement from the hydrophobic pocket and the surface exposure of the myristoyl moiety resulting in enhanced CHP3 binding to lipid membranes in both Ca²⁺- and Mg²⁺-bound states.