State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.
Protein Sci. 2019 Oct;28(10):1819-1829. doi: 10.1002/pro.3696. Epub 2019 Aug 9.
Fstl1 is a TGF-β superfamily binding protein which involved in many pathological processes. The function of Fstl1 has been widely elucidated, but its structural characterization has not been explored. Here we solved the high-resolution crystal structure of FK domain of murine Fstl1, analyzed its unique characteristics, and investigated its contribution to the function of full-length Fstl1. We found that Fstl1-FK forms a stable dimer in both solution and crystal, which suggest that this protein may function as a dimer during its interaction with TGF-β, a molecule known to form dimer during activation process. We also found this FK domain is indispensable for the proper function of Fstl1 during the transduction of TGF-β signaling. These observations provide important insights into the understanding of Fstl1 and may facilitate the exploration of this molecule in clinical study.
Fstl1 是 TGF-β 超家族结合蛋白，参与许多病理过程。Fstl1 的功能已经被广泛阐明，但它的结构特征尚未被探索。在这里，我们解析了鼠 Fstl1 FK 结构域的高分辨率晶体结构，分析了其独特的特征，并研究了它对全长 Fstl1 功能的贡献。我们发现 Fstl1-FK 在溶液和晶体中均形成稳定的二聚体，这表明该蛋白在与 TGF-β相互作用时可能作为二聚体发挥作用，TGF-β在激活过程中形成二聚体。我们还发现该 FK 结构域对于 Fstl1 在 TGF-β 信号转导过程中的正常功能是不可或缺的。这些观察结果为理解 Fstl1 提供了重要的见解，并可能有助于在临床研究中探索该分子。
