Synaptic adhesion molecules play a crucial role in the regulation of synapse development and maintenance. Recently, several families of leucine-rich repeat (LRR) domain-containing neuronal adhesion molecules have been characterised, including netrin-G ligands, LRRTMs and the synaptic adhesion-like molecule (SALM) family proteins. Most of these are expressed at the excitatory glutamatergic synapses, and dysfunctions of these genes are genetically linked with cognitive disorders, such as autism spectrum disorders and schizophrenia. The SALM family proteins SALM3 and SALM5, similar to SLITRKs, have been shown to bind to the presynaptic receptor protein tyrosine phosphatase (RPTP) family ligands. Here, we present the 3.1 Å crystal structure of the SALM5 LRR-Ig-domain construct and biophysical studies that verify the crystallographic results. We show that SALM1, SALM3 and SALM5 form similar dimeric structures, in which the LRR domains form the dimer interface. Both SALM3 and SALM5 bind to RPTP immunoglobulin domains with micromolar affinity. SALM3 shows a clear preference for the RPTP ligands with the meB splice insert. Our structural studies and sequence conservation analysis suggests a ligand-binding site and mechanism for RPTP binding via the dimeric LRR domain region.

中文翻译：

---

SALM5的结构建议用于突触前RPTP配体识别的二聚体组装。

突触粘附分子在调节突触的发生和维持中起着至关重要的作用。近来，已表征了多个含亮氨酸重复序列（LRR）域的神经元粘附分子家族，包括netrin-G配体，LRRTM和突触粘附样分子（SALM）家族蛋白。这些基因中的大多数在兴奋性谷氨酸能突触中表达，并且这些基因的功能障碍与认知障碍（例如自闭症谱系障碍和精神分裂症）遗传相关。与SLITRKs相似，已显示SALM家族蛋白SALM3和SALM5与突触前受体蛋白酪氨酸磷酸酶（RPTP）家族配体结合。在这里，我们介绍SALM5 LRR-Ig结构域构建体的3.1Å晶体结构，以及验证晶体学结果的生物物理研究。我们显示SALM1，SALM3和SALM5形成相似的二聚体结构，其中LRR域形成二聚体界面。SALM3和SALM5都以微摩尔亲和力结合RPTP免疫球蛋白结构域。SALM3对带有meB剪接插入物的RPTP配体表现出明显的偏爱。我们的结构研究和序列保守性分析表明，配体结合位点和通过二聚体LRR结构域区域进行RPTP结合的机制。