Brown Kyle L, Cummings Christopher F, Vanacore Roberto M, Hudson Billy G
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, 37232.
Center for Structural Biology, Vanderbilt University Medical Center, Nashville, Tennessee, 37232.
Protein Sci. 2017 Nov;26(11):2151-2161. doi: 10.1002/pro.3283.
Collagen IV scaffolds assemble through an intricate pathway that begins intracellularly and is completed extracellularly. Multiple intracellular enzymes act in concert to assemble collagen IV protomers, the building blocks of collagen IV scaffolds. After being secreted from cells, protomers are activated to initiate oligomerization, forming insoluble networks that are structurally reinforced with covalent crosslinks. Within these networks, embedded binding sites along the length of the protomer lead to the "decoration" of collagen IV triple helix with numerous functional molecules. We refer to these networks as "smart" scaffolds, which as a component of the basement membrane enable the development and function of multicellular tissues in all animal phyla. In this review, we present key molecular mechanisms that drive the assembly of collagen IV smart scaffolds.
IV型胶原蛋白支架通过一个复杂的途径组装而成，该途径始于细胞内并在细胞外完成。多种细胞内酶协同作用以组装IV型胶原蛋白原聚体，即IV型胶原蛋白支架的构建单元。从细胞分泌后，原聚体被激活以启动寡聚化，形成通过共价交联进行结构增强的不溶性网络。在这些网络中，沿原聚体长度嵌入的结合位点导致IV型胶原蛋白三螺旋被众多功能分子“修饰”。我们将这些网络称为“智能”支架，作为基底膜的一个组成部分，它能够使所有动物门中的多细胞组织得以发育和发挥功能。在这篇综述中，我们介绍了驱动IV型胶原蛋白智能支架组装的关键分子机制。
