人Dispathced-1 结构为 Hedgehog 配体生物发生提供了线索。
Structure of human Dispatched-1 provides insights into Hedgehog ligand biogenesis.
机构信息
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA
出版信息
Life Sci Alliance. 2020 Jul 9;3(8). doi: 10.26508/lsa.202000776. Print 2020 Aug.
Hedgehog (HH) signaling is essential for metazoan development. The HH ligand is secreted into the extracellular space by a cell surface protein named Dispatched-1 (DISP1). Here, we report the cryo-EM structure of human DISP1 protein. DISP1 contains 12 transmembrane helices (TMs) and two extracellular domains (ECDs). Its ECDs reveal an open state, in contrast to its structural homologues PTCH1 and NPC1, whose extracellular/luminal domains adopt a closed state. The low-resolution structure of the DISP1 complex with dual lipid-modified HH ligand reveals how the ECDs of DISP1 engage with HH ligand. Moreover, several cholesterol-like molecules are found in the TMs, implying a transport-like function of DISP1.
刺猬（HH）信号对于后生动物的发育至关重要。HH 配体由一种名为 Dispatched-1（DISP1）的细胞表面蛋白分泌到细胞外空间。在这里，我们报告了人 DISP1 蛋白的冷冻电镜结构。DISP1 包含 12 个跨膜螺旋（TMs）和两个细胞外结构域（ECDs）。它的 ECD 呈现开放状态，与结构同源物 PTCH1 和 NPC1 形成对比，后者的细胞外/腔域采用封闭状态。具有双脂修饰 HH 配体的 DISP1 复合物的低分辨率结构揭示了 DISP1 的 ECD 如何与 HH 配体结合。此外，在 TMs 中发现了几种类似胆固醇的分子，这暗示了 DISP1 的运输样功能。
Zotero 插件