FIGURE 1.

LRRK2 domain structure and proposed function as a GAD GTPase. (A) The domain structure of LRRK2 and location of key pathogenic mutations and PD risk variants (^∗) is depicted. Note the central catalytic core consisting of the RocCOR tandem and kinase domains. (B) The assumed behavior of the LRRK2 RocCOR tandem as a GAD protein is represented graphically. In this model, COR domains are a constitutive dimerization device, whilst Roc domains cycle between a GDP-bound and monomeric ‘off’ state, and a GTP-bound and dimeric ‘on’ state.