Semaphorin ligands interact with plexin receptors to contribute to functions in the development of myriad tissues including neurite guidance and synaptic organisation within the nervous system. Cell‐attached semaphorins interact in trans with plexins on opposing cells, but also in cis on the same cell. The interplay between trans and cis interactions is crucial for the regulated development of complex neural circuitry, but the underlying molecular mechanisms are uncharacterised. We have discovered a distinct mode of interaction through which the Drosophila semaphorin Sema1b and mouse Sema6A mediate binding in cis to their cognate plexin receptors. Our high‐resolution structural, biophysical and in vitro analyses demonstrate that monomeric semaphorins can mediate a distinctive plexin binding mode. These findings suggest the interplay between monomeric vs dimeric states has a hereto unappreciated role in semaphorin biology, providing a mechanism by which Sema6s may balance cis and trans functionalities.

中文翻译：

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信号蛋白-丛蛋白顺式相互作用的结构基础。


信号蛋白配体与丛蛋白受体相互作用，有助于多种组织发育的功能，包括神经系统内的神经突引导和突触组织。细胞附着的信号蛋白与相对细胞上的丛蛋白以反式相互作用，但也在同一细胞上以顺式相互作用。反式和顺式相互作用之间的相互作用对于复杂神经回路的调节发展至关重要，但潜在的分子机制尚不清楚。我们发现了一种独特的相互作用模式，通过这种模式，果蝇信号蛋白 Sema1b 和小鼠 Sema6A 介导顺式与其同源丛蛋白受体的结合。我们的高分辨率结构、生物物理和体外分析表明单体信号蛋白可以介导独特的丛蛋白结合模式。这些发现表明单体与二聚体状态之间的相互作用在信号蛋白生物学中具有迄今为止未被认识到的作用，提供了 Sema6s 可以平衡顺式和反式功能的机制。