(A) Superposition of the crystal structures of 14 Rab isoforms (Rab1a, 1b, 2, 3, 4, 6, 7, 9, 12, 18, 27, 30, 31, 43). All potential LRRK2 phosphorylation sites (in grey) cluster in the same region. (B) MS analysis of in vitro phosphorylated Rab10 identified three LRRK2-specific sites (note that phosphorylation is prevented completely by HG-10-102-01) and pT73 as the one with the highest intensity. The collosion-induced dissociation (CID) fragmentation spectrum and the Andromeda score (score) (Cox et al., 2011 ) for the tryptic pT73-Rab10 peptide are shown. (C) Phosphorylation of Rab8a and Rab1b by LRRK2-wt. Inhibition of LRRK2 by HG-10-102-01 prevents phosphorylation. (D) HPLC trace of tryptic peptides of Rab8a and Rab1b (E) after in vitro phosphorylation by LRRK2-wt and sequence analysis of tryptic peptides. Y axis units are relative Cherenkov counts per minute. MS, mass spectrometry; wt, wild type.