The guidance and adhesion protein FLRT2 dimerizes in cis via dual Small-X3-Small transmembrane motifs
| Autor: | Verity Jackson, Julia Hermann, Christopher J. Tynan, Daniel J. Rolfe, Robin A. Corey, Anna L. Duncan, Maxime Noriega, Amy Chu, Antreas C. Kalli, E. Yvonne Jones, Mark S. P. Sansom, Marisa L. Martin-Fernandez, Elena Seiradake, Matthieu Chavent |
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| Přispěvatelé: | Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
010304 chemical physics biology Cell adhesion molecule Chemistry 01 natural sciences [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation Transmembrane protein Cell biology Protein–protein interaction Fibronectin [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biophysics 03 medical and health sciences Transmembrane domain Cell surface receptor Structural Biology 0103 physical sciences biology.protein Trans-acting Receptor Molecular Biology 030304 developmental biology |
| Popis: | 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.FieldsStructural Biology and Biophysics / Computational Biology |
| Databáze: | OpenAIRE |
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