Fig. 9: An autoinhibitory S2S^kin_dimer sub-unit promotes hetero^conf-oligomer growth.

a Tetramer that would form after inhibiting B2B^ect/H2H^kin_dimer sub-units or Lzip contacts with two Bb2Bb^kin_interfaces buttressing an Asym^kin_dimer sub-unit. Ectodomains and kinases belonging to the same receptor in H2H^ect_dimer/2x^kin_monomers sub-units are colored accordingly. b Ligand-free hetero^conf-oligomer model incorporating four S2S^kin_interfaces. c Left, side-view of the S2S^kin_dimer sub-unit maintained mainly through the β2-sheet and αD-helix of the one monomer and the αE- and αΙ-helices of another (PDB ID: 5CNO [https://www.rcsb.org/structure/5CNO])⁴⁸. The position of the A-loop in the inactive configuration is marked. Right, cartoon representation of the top-view of an H2H^kin_dimer sub-unit flanked by two monomers via S2S^kin_interfaces. d, g, h FLImP analysis of 100 separation probability distributions between Affibody-CF640R pairs in the conditions indicated: Sum of posteriors of individual separations between fluorophores (gray background) and abundance-weighted probability distributions of individual components of decomposed separation distribution (colored peaks). Plot legend and bars above colored component distributions give the median and most-compact 68% confidence interval for each. Legend also gives median proportion of measurements assigned to clutter. The median peak positions marked by dashed lines are those of WT-EGFR. e Comparisons between decomposed separation probability distributions between datasets. The continuous lines show the marginalized separation posterior, i.e. the sum of the abundance-weighted peaks, for each condition in the inset. The fluctuations around each continuous line arise from variations derived from FLImP decompositions for 20 bootstrap-resampled datasets to assess errors due to finite number of measurements. Dashed lines marked WT-EGFR median peak positions (as in d). Colored arrows show shift from WT-EGFR. f Wasserstein MDS analysis of FLImP decompositions for the conditions in the inset. Similarities or dissimilarities between the 21 separation sets of different conditions (one main FLImP decomposition plus 20 bootstrap-resampled decompositions) are compared. The plot axes are components C1 and C2. C1 represents the dimension that captures the largest amount of variance in the data, while C2 represents the second-largest amount of variance that is orthogonal to C1. The ellipse centers (95% confidence range) mark the positions of the main FLImP decompositions. The crosses mark the positions of individual bootstrap-resampled separation sets.