Figure 1.

(A) Domain architecture of human LRRK2 with its respective amino acid positions. ARM: Armadillo repeats region; ANK: Ankyrin repeat region; LRR: leucine-rich repeats; ROC: Ras-of-complex GTPase domain; COR: C-terminal-of-ROC domain; Kinase: protein tyrosine kinase-like domain; WD40: WD40 repeat. The detailed functional partition of ROC is depicted above with the guanine nucleotide phosphate-binding loop (P-loop), Switch I and Switch II, and G4 and G5 loop highlighted in green rectangles. The residue position R1441 is highlighted with a red arrow. (B) Cartoon model of ROC monomer roughly divided into head (including β1, α1, β2, and β3), neck (including α2) and body (including β4, α3, β5, α4, β6, and α5) subdomains. The monomer is colored based on a secondary structure, and the P-loop, Switch I, Switch II, G4 loop, and G5 loop are highlighted in light green, hot pink, purple, brown, and gold, respectively. Residue R1441 is highlighted. (C) Schematic model of ROC dimer–monomer dynamic transition during nucleotide turnover based on GAD theory. (D) Cartoon model of ROCs-GDP, the two monomers are shown in pink (ROC^A) and green (ROC^B), respectively. (E) Molecular surface representation of ROC dimer highlighting the nucleotide-binding pockets (blue-dashed oval). Gnt1 is accommodated by ROC^A head and ROC^B body, while Gnt2 interacts with ROC^A body and ROC^B head. Unless otherwise specified, the graphs showing ROCs overview in our work will all be presented from this perspective with Gnt1 residing on the top-left. The presumed compact functional units are denoted as ROCs1 and ROCs2.