Fig. 7: The extracellular structure of ligand-free heteroconf-oligomers.
a Top left, Tetramer assembled by an H2Hect/2xkinmonomers sub-unit and a B2Bect/H2Hkindimer sub-unit. A transmembrane monomer of an H2Hect/2xkinmonomers interacts with the transmembrane dimer of the B2Bect/H2Hkindimer via an Lzip interface. The Lzip interface is related to the transmembrane dimers in the B2Bect/H2Hkindimer sub-unit and St2Stect/Asymkindimer sub-unit by a rotation of the helix along the long axis45. Bottom left, two tetramers form a St2Stect/Asymkindimer sub-unit. Note that the latter could in principle form also from one H2Hect/2xkinmonomers sub-unit forming an Lzip interface with a tetramer made of one H2Hect/2xkinmonomers sub-unit and a B2Bect/H2Hkindimer sub-unit. (Attempts to join a H2Hectdimer/2xkinmonomers sub-unit and a St2Stect/Asymkindimer sub-unit via Lzip contacts led to steric clashes. More details in Supplementary Fig. 4). Right, Annotated interfaces in the model. b–h Seven distinct optimally grouped triangles from 2D FLImP separations determined between EGF-CF640R probes bound to cell surface T766M-EGFR (Supplementary Fig. 5). The side lengths of each triangle are annotated in each inset in the colors used in 1D FLImP decompositions when found in the separation sets of either T766M-EGFR or WT-EGFR (Fig. 4a, d), and colored and underlined if found in both. Separations >70 nm are outside the range of 1D FLImP. The abundance of each triangle (T1-7) is stated bottom right. i Ligand-free heteroconf-oligomer model extended as described in a. The approximate positions where EGF-CF640R would bind DIII of the ectodomains are marked (red circles). Four versions of (b), the experimentally-optimized triangle 1 within errors (T1a-T1d), are superimposed. Inset, table of the side lengths of the superimposed triangles. j Top, ligand-free heteroconf-oligomer model with the triangle groups T2-T4 (c–e) superimposed. Bottom, heteroconf-oligomer model with the largest triangles T5-T7 (f–h) superimposed. Inset, table of the side lengths of the superimposed triangles.
