The members of the CCN (Cyr61/CTGF/Nov) family are a group of matricellular regulatory proteins that are essential to a wide range of functional pathways in cell signalling. Through interacting with extracellular matrix components and growth factors via one of their four domains, the CCN proteins are involved in critical biological processes such as angiogenesis, cell proliferation, bone development, fibrogenesis and tumorigenesis. Here, the crystal structure of the thrombospondin module 1 (TSP1) domain of CCN3 (previously known as Nov) is presented, which shares a similar three‐stranded fold with the thrombospondin type 1 repeats of thrombospondin‐1 and spondin‐1, but with variations in the disulfide connectivity. Moreover, the CCN3 TSP1 domain lacks the typical π‐stacked ladder of charged and aromatic residues on one side of the domain that is seen in other TSP1 domains. Using conservation analysis among orthologous domains, it is shown that a charged cluster in the centre of the domain is the most conserved site and this cluster is predicted to be a potential functional epitope for heparan sulfate binding. This variant TSP1 domain has also been used to revise the sequence determinants of TSP1 domains and to derive improved Pfam sequence profiles for the identification of novel TSP1 domains in more than 10 000 proteins across diverse phyla.

中文翻译：

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基质细胞蛋白CCN3的血小板反应蛋白模块1结构域显示出非典型的二硫键模式和不完整的CWR层。

CCN（Cyr61 / CTGF / Nov）家族的成员是一组基质细胞调节蛋白，这些蛋白对于细胞信号传导中的各种功能途径必不可少。通过其四个域之一与细胞外基质成分和生长因子相互作用，CCN蛋白参与了关键的生物学过程，例如血管生成，细胞增殖，骨骼发育，纤维生成和肿瘤发生。此处展示了CCN3​​的血小板反应蛋白模块1（TSP1）域（以前称为Nov）的晶体结构，与血小板反应蛋白1和海绵体蛋白1的血小板反应蛋白1型重复序列共享相似的三链折叠。二硫键连接性的变化。此外，CCN3 TSP1域缺乏在其他TSP1域中看到的，在域的一侧典型的带电荷和芳香族残基的典型π堆叠阶梯。使用直向同源结构域之间的保守性分析，表明在结构域中心的带电荷簇是最保守的位点，并且该簇被预测为硫酸乙酰肝素结合的潜在功能性表位。该变体TSP1结构域也已用于修订TSP1结构域的序列决定簇，并获得改进的Pfam序列图谱，用于鉴定跨不同门的10000种蛋白质中的新型TSP1结构域。结果表明，结构域中心的带电簇是最保守的位点，预计该簇是硫酸乙酰肝素结合的潜在功能性表位。该变体TSP1结构域也已用于修订TSP1结构域的序列决定簇，并获得改进的Pfam序列图谱，用于鉴定跨不同门的10000种蛋白质中的新型TSP1结构域。结果表明，结构域中心的带电簇是最保守的位点，预计该簇是硫酸乙酰肝素结合的潜在功能性表位。该变体TSP1结构域也已用于修订TSP1结构域的序列决定簇，并获得改进的Pfam序列图谱，用于鉴定跨不同门的10000种蛋白质中的新型TSP1结构域。