Table 1.

The effect of PD-causing mutations in the LRRK2 RocCOR tandem domain on GTP-binding and GTPase activity.

Mutation	LRRK2 construct	GTP binding	GTP hydrolysis	Prediction	Reference
N1437H	Full length	↑	ns	↑ GTP-bound	Aasly et al., 2010
R1441C	Full length	↑	ns	↑ GTP-bound	West et al., 2007
R1441C	Full length	—	↓	↑ GTP-bound	Li et al., 2007
R1441C	Full length	—	↓	↑ GTP-bound	Lewis et al., 2007
R1441C	Roc	ns	↓	↑ GTP-bound	Deng et al., 2008
R1441C	Full length	ns	↓	↑ GTP-bound	Xiong et al., 2010
R1441C	Roc, COR, kinase	—	—	No change	Xiong et al., 2010
R1441C	970-2527	ns	↓	↑ GTP-bound	Pungaliya et al., 2010
R1441C	Full length	↑	ns	↑ GTP-bound	Stafa et al., 2012
R1441G	Full length	↑	ns	↑ GTP-bound	West et al., 2007
R1441G	Full length	—	↓	↑ GTP-bound	Li et al., 2007
R1441G	Full length	ns	↓	↑ GTP-bound	Xiong et al., 2010
R1441H	Roc	↑	↓	↑ GTP-bound	Liao et al., 2014
“R1441”A	C. tepidum RocCOR	—	↓	↑ GTP-bound	Gotthardt et al., 2008
Y1699C	Full length	↑	ns	↑ GTP-bound	West et al., 2007
Y1699C	Full length	ns	↓	↑ GTP-bound	Xiong et al., 2010
Y1699C	Full length	—	↓	↑ GTP-bound	Daniëls et al., 2011
Y1699C	Full length	↑	ns	↑ GTP-bound	Stafa et al., 2012
“Y1699”C	C. tepidum RocCOR	—	↓	↑ GTP-bound	Gotthardt et al., 2008

Based on published data, the pathogenic N1437H, R1441C, R1441G, R1441H, and Y1699C mutations all elicit an increase in the fraction of GTP-bound LRRK2. Only one construct, an R1441C RocCOR-kinase, displayed no changes in GTP-binding or GTP hydrolysis; however, this mutation decreased GTPase activity in full length LRRK2 in the same publication. Note that mutations at residues equivalent to R1441 and Y1699 in C. tepidum Roco protein produce consistent results. Key: up and down arrows represent increases and decreases, respectively; dashes represent no change; ‘ns’ indicates ‘not studied.’