Fig. 8: Alternatively spliced insert within the β-propeller mediates the TEN2 +SS dimer interface.

a Structure of TEN2 +SS dimer shows the splice inserts from each protomer (yellow and magenta residues) creates a binding interface and leads to TEN2 dimerization via the β-propeller. Close-up views of the dimer interface show two salt bridges and five hydrogen bonds are at the interface. One of the salt bridges is directly mediated by the glutamate (E1306) within the splice insert NKEFKHS and four of the hydrogen bonds also require splice site residues. Two salt bridges align almost parallel to each other and to the disulfide bonds between the EGF repeats and restricts the conformational flexibility of the TEN2 head significantly (see Fig. 9). The N-termini of both protomers face the same direction towards the EGF repeats, and thus, the dimer is positioned as a cis-dimer that will extend the zippering of the already existing EGF-mediated cis-dimer, although it was reported to form as a trans-homodimer, previously³⁸. TEN protomers (PDB: 6FB3) are colored as cyan and palegreen, respectively, and splice sites are colored as yellow and magenta, respectively. b Cell-aggregation experiments show the LPHN3 binding ability of TEN2 +SS is partially restored when the two salt bridges are broken in the TEN2 +SS mutant (*P ≤ 0.05; ***P ≤ 0.001; by one-way ANOVA). Data are presented as mean ± SEM, n = 3, and are representative of at least three independent experiments. Source data are provided as a Source Data file.