TY - JOUR T1 - The guidance and adhesion protein FLRT2 dimerizes <em>in cis</em> via dual Small-X<sub>3</sub>-Small transmembrane motifs JF - bioRxiv DO - 10.1101/2020.10.06.328401 SP - 2020.10.06.328401 AU - Verity Jackson AU - Julia Hermann AU - Christopher J. Tynan AU - Daniel J. Rolfe AU - Robin A. Corey AU - Anna L. Duncan AU - Maxime Noriega AU - Amy Chu AU - Antreas C. Kalli AU - E. Yvonne Jones AU - Mark S. P. Sansom AU - Marisa L. Martin-Fernandez AU - Elena Seiradake AU - Matthieu Chavent Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/08/02/2020.10.06.328401.abstract N2 - Fibronectin Leucine-rich Repeat Transmembrane (FLRT 1-3) proteins are a family of broadly expressed single-spanning transmembrane receptors that play key roles in development. Their extracellular domains mediate homotypic cell-cell adhesion and heterotypic protein interactions with other receptors to regulate cell adhesion and guidance. These in trans FLRT interactions determine the formation of signaling complexes of varying complexity and function. Whether FLRTs also interact at the surface of the same cell, in cis, remains unknown. Here, molecular dynamics simulations reveal two dimerization motifs in the FLRT2 transmembrane helix. Single particle tracking experiments show that these ‘Small-X3-Small’ motifs synergize with a third dimerization motif encoded in the extracellular domain to permit the cis association and co-diffusion patterns of FLRT2 receptors on cells. These results may point to a competitive switching mechanism between in cis and in trans interactions which suggests that homotypic FLRT interaction mirrors the functionalities of classic adhesion molecules.Fields Structural Biology and Biophysics / Computational BiologyCompeting Interest StatementThe authors have declared no competing interest. ER -