Extended Data Fig. 7: Properties of the microtubule-associated LRRK2^RCKW filaments.

a, b, The LRRK2^RCKW structure solved in this work (a) was split at the junction between the N- and C-lobes of the kinase domain (L1949-A1950) (b). c, Docking of the two halves of LRRK2^RCKW into a cryo-EM map of a LRRK2^RCKW dimer solved in the presence of MLi-2. The dimer map is the same one shown in Fig. 3 and Extended Data Figs. 10 and 11. d, The model obtained in c was docked into cryo-EM maps of either WD40- or COR-mediated dimers obtained in the presence of MLi-2. e, Molecular models resulting from the docking in d. f, Aligning, in alternating order, copies of the dimer models generated in d and e results in a right-handed filament with dimensions compatible with those of a microtubule, and its ROC domains pointing inwards (see Fig. 3g, h for more details). g, Docking of the two halves of LRRK2^RCKW into a cryo-EM map of a LRRK2^RCKW monomer solved in the absence of inhibitor (apo). The map is the one shown in Fig. 1g and Extended Data Fig. 6. h, Three-way comparison of LRRK2^RCKW (with domain colours) and the models resulting from the dockings into the MLi-2 WD40-mediated dimer map (c) (dark blue) and apo monomer map (g) (light blue). The three structures were aligned using the C-lobes of their kinases and the WD40 domain. The superposition illustrates that the docking into the apo map results in a structure very similar to that obtained from the trimer (Fig. 1) and that the presence of MLi-2 leads to a closing of the kinase. i, Molecular model of the microtubule-associated LRRK2^RCKW filament obtained by docking a fragment of a microtubule structure (PDB code 6O2S) into the corresponding density in the sub-tomogram average (Fig. 2a). j, Same view as in i with the models shown as surface representations coloured by their Coulomb potential. k, l, ‘Peeling off’ of the structure shown in j, with the LRRK2^RCKW filament seen from the perspective of the microtubule surface (k) and the microtubule surface seen from the perspective of the LRRK2^RCKW filament (l). Note that the acidic C-terminal tubulin tails are not ordered in the microtubule structure and are therefore not included in the surface charge distributions. The Coulomb potential colouring scale is shown on the right.