Jackson, V, Hermann, J, Tynan, CJ et al. (11 more authors) (2022) The guidance and adhesion protein FLRT2 dimerizes in cis via dual small-X3-small transmembrane motifs. Structure, 30 (9). pp. 1354-1365. ISSN 0969-2126
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2022 Elsevier Ltd. This is an author produced version of an article published in Structure. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | FLRT, molecular dynamics simulations, coarse grain, single molecule tracking, small-X3-small motif, in cis interactions, MINFLUX localisation |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 31 May 2022 15:25 |
Last Modified: | 13 Jun 2023 00:13 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.str.2022.05.014 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:187499 |
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