Takjoo Rozita, Wilson David T, Le Quilliec Justine, Schmidt Casey A, Zhao Guangzu, Liddell Michael J, Shaikh Naeem Y, Sunagar Kartik, Loukas Alex, Smout Michael J, Daly Norelle L
Australian Institute of Tropical Health and Medicine, James Cook University, Cairns, Australia.
Univ Brest, École Supérieure d'Ingénieurs en Agroalimentaire de Bretagne atlantique, Plouzané, France.
FEBS Open Bio. 2025 Mar;15(3):415-426. doi: 10.1002/2211-5463.13931. Epub 2024 Nov 19.
Sea stars are an abundant group of marine invertebrates that display remarkably robust regenerative capabilities throughout all life stages. Numerous proteins and peptides have been identified in a proteome study on the coelomic fluid (biofluid) of the common sea star Asterias rubens, which appear to be involved with the wound-healing response in the organism. However, the three-dimensional structure and function of several of these injury-responsive peptides, including the peptide KASH2, are yet to be investigated. Here, we show that the KASH2 peptide adopts a disulfide-directed β-hairpin fold (DDH). The DDH motif appears to be evolutionarily related to the inhibitor cystine knot motif, which is one of the most widespread disulfide-rich peptide folds. The DDH motif was originally thought to be restricted to arachnids, but our study suggests that as a result of convergent evolution it could also have originated in sea stars. Although the widely conserved DDH fold has potential cross-phyla wound-healing capacity, we have shown that KASH2 does not enhance the proliferation of human fibroblasts, a simple method for wound-healing re-epithelialisation screening. Therefore, additional research is necessary to determine the role of KASH2 in the sea stars.
海星是一类数量丰富的海洋无脊椎动物，在其整个生命阶段都表现出极强的再生能力。在一项针对常见海星红海星（Asterias rubens）体腔液（生物体液）的蛋白质组研究中，已鉴定出许多蛋白质和肽，它们似乎参与了该生物体的伤口愈合反应。然而，包括KASH2肽在内的几种损伤反应性肽的三维结构和功能尚未得到研究。在此，我们表明KASH2肽呈现出二硫键导向的β-发夹折叠（DDH）。DDH基序似乎在进化上与抑制剂胱氨酸结基序相关，后者是分布最广泛的富含二硫键的肽折叠之一。DDH基序最初被认为仅限于蛛形纲动物，但我们的研究表明，由于趋同进化，它也可能起源于海星。尽管广泛保守的DDH折叠具有潜在的跨门类伤口愈合能力，但我们已表明KASH2并不能增强人类成纤维细胞的增殖，而成纤维细胞增殖是伤口愈合再上皮化筛选的一种简单方法。因此，有必要进行更多研究以确定KASH2在海星中的作用。
