The guidance and adhesion protein FLRT2 dimerizes in cis via dual small-X3-small transmembrane motifs.
The guidance and adhesion protein FLRT2 dimerizes in cis via dual small-X3-small transmembrane motifs.
复制标题
引导和粘附蛋白 FLRT2 通过双小 X3 小跨膜基序顺式二聚化。
DOI：
10.1016/j.str.2022.05.014
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Jackson V
中科院分区：
文献类型：
--
作者：
Jackson V
富含亮氨酸重复序列的纤维连接蛋白跨膜蛋白(flt 1-3)是一个广泛表达的单跨膜受体家族，在发育过程中起着关键作用。它们的胞外结构域介导同型细胞-细胞黏附和异型蛋白质与其他受体的相互作用，以调节细胞黏附和引导。这些跨FLRT相互作用决定了不同复杂性和功能的信号复合体的形成。目前尚不清楚Flrt是否也在同一细胞的表面相互作用。在这里，分子动力学模拟揭示了Flrt2跨膜螺旋中的两个二聚化基序。单粒子跟踪实验表明，这些小-X3-小基序与编码在细胞外域的第三个二聚基序协同作用，允许细胞上Flrt2受体的结合和共扩散模式。这些结果可能指出了顺式和反式相互作用之间的竞争性转换机制，这表明同型FLRT相互作用反映了经典黏附分子的功能。
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. Thesein transFLRT 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 thecisassociation and co-diffusion patterns of FLRT2 receptors on cells. These results may point to a competitive switching mechanism betweenin cisandin transinteractions, which suggests that homotypic FLRT interaction mirrors the functionalities of classic adhesion molecules.