Extended Data Fig. 4: Comparison between LRRK2^RCKW and integrative models built into cryo-ET maps of LRRK2 filaments in cells and docking of LRRK2^RCKW into those maps.

a, Root-mean-square deviation (r.m.s.d.) between the atomic model of LRRK2^RCKW and each of the 1,167 integrative models previously generated⁵. r.m.s.d. values were calculated in Chimera⁶² using 100% residue similarity and with pruning iterations turned off. r.m.s.d. values are grouped into 53 clusters of related models (see ref. ⁵ for details), with the mean and standard deviation shown whenever the cluster contains two or more models. Integrative models that gave the lowest, median and highest r.m.s.d. values are shown. The models are coloured according to the per-residue r.m.s.d. with the atomic model of LRRK2^RCKW. b, The WD40s in the crystal structure of a dimer of the LRRK2 WD40 (PDB code: 6DLP)⁹ were replaced with the WD40s from our cryo-EM structure of LRRK2^RCKW. c, The resulting dimer was fitted into the 14 Å cryo-ET map of cellular microtubule-associated LRRK2 filaments⁵. d, Two views of the same fitting shown in c, displayed with a higher threshold for the map to highlight the fitting of the WD40 β-propellers into the density. The white arrows point towards the holes at the centre of the β-propellers densities. e, Four copies of LRRK2^RCKW were docked into the cryo-ET map by aligning their WD40 domains to the docked WD40 dimer. f, Model containing the four aligned LRRK2^RCKW. g–j, Modelling of the kinase-closed form of LRRK2^RCKW. g, h, The structure of ITK bound to an inhibitor (PDB code 3QGY)⁶³, which is in a closed conformation, was aligned to LRRK2^RCKW using only the C-lobes of the two kinases. i, The N-terminal portion of LRRK2^RCKW, comprising ROC, COR-A, COR-B and the N-lobe of the kinase, was aligned to ITK using only the N-lobes of the kinases. ROC, COR-A and COR-B were moved as a rigid body in this alignment. j, Kinase-closed model of LRRK2^RCKW.