Extended Data Fig. 6: Cryo-EM analysis of a monomer and WD40- and COR-mediated dimers of LRRK2^RCKW in the absence of inhibitor (apo) and dimerization of LRRK2^RCKW outside the filaments.

a, Data-processing strategy for obtaining cryo-EM structures of a monomer and WD40- and COR-mediated dimers of LRRK2^RCKW in the absence of inhibitor. The models used during the processing of the dimers (Methods) are those shown in Extended Data Fig. 5d, along with an additional linear trimer (Methods) used for particle sorting. The models used for processing of the monomer (Methods) were the same dimer models as in Extended Data Fig. 5d (used for particle sorting) in addition to a monomer model generated from our LRRK2^RCKW model (used for refinement). b, Two-dimensional (2D) class averages of WD40- and COR-mediated LRRK2^RCKW dimers obtained in the absence of inhibitors (apo) or in the presence of either ponatinib or MLi-2. The same molecular models of the two dimers shown in Fig. 3 are shown on the left but in orientations similar to those represented by the 2D class averages shown here. For each class average, a projection from the corresponding model in the best-matching orientation is shown to its left. c, Two copies of the LRRK2^RCKW structure were aligned to the ROC–COR domains of the LRR–ROC–COR structure from the C. tepidum Roco protein (PDB code 6HLU) to replicate the interface observed in the bacterial homologue in the context of the human protein. This panel shows a comparison between the dimer modelled based on the C. tepidum LRR–ROC–COR structure and the dimer observed for LRRK2^RCKW in this work. Although the bacterial structure shows a dimerization interface that involves the GTPase (ROC), LRRK2^RCKW interacts exclusively through its COR-A and -B domains, with the ROC domains located away from this interface. The two arrangements are shown schematically in cartoon form below the structures.