LRRK2 Tools for Advancing Parkinson’s Disease Research

Figure 1. LRRK2 mutations and domains: The above ideogram depicts the full-length, 2527 amino acid, LRRK2 protein and its domains: ankyrin-like repeats (ANK), leucine-rich repeats (LRR), Ras of complex protein, GTPase domain (ROC), C-terminal of ROC domain (COR), kinase domain (kinase), and WD40 repeats domain (WD40).   Also, depicted are four variants available from Life Technologies: G2019S, the most common Parkinson’s disease (PD) segregating polymorphism, which is associated with increased kinase activity; I2020T also segregates with PD, but the functional effect is unknown; D1994A is an engineered variant that renders the kinase inactive; R1441C is a natural PD segregating variant, which is suspected to decrease GTPase activity. S935, shown in grey, indicates an internal phosphorylation site, against which specific antibodies have been generated. Truncated proteins span amino acids 970-2527, and do not contain the N-terminus, ANK domain, nor the internal S935 phosphorylation site. For more information regarding LRRK2 see Nature Reviews Neuroscience (2010), v11, pp791-797.