Yamagata M, Yamada K M, Yamada S S, Shinomura T, Tanaka H, Nishida Y, Obara M, Kimata K
Institute for Molecular Science of Medicine, Aichi Medical University, Japan.
J Cell Biol. 1991 Oct;115(1):209-21. doi: 10.1083/jcb.115.1.209.
Extracellular matrix molecules are generally categorized as collagens, elastin, proteoglycans, or other noncollagenous structural/cell interaction proteins. Many of these extracellular proteins contain distinctive repetitive modules, which can sometimes be found in other proteins. We describe the complete primary structure of an alpha 1 chain of type XII collagen from chick embryonic fibroblasts. This large, structurally chimeric molecule identified by cDNA analysis combines previously unrelated molecular domains into a single large protein 3,124 residues long (approximately 340 kD). The deduced chicken type XII collagen sequence starts at the amino terminus with one unit of the type III motif of fibronectin, which is followed by one unit homologous to the von Willebrand factor A domain, then one more fibronectin type III module, a second A domain from von Willebrand factor, 6 units of type III motif and a third A domain, 10 consecutive units of type III motif and a fourth A domain, a domain homologous to the NC4 domain peptide of type IX collagen, and finally two short collagenous regions previously described as part of the partially sequenced collagen type XII molecule; an Arg-Gly-Asp potential cell adhesive recognition sequence is present in a hydrophilic region at the terminus of one collagenous domain. Antibodies raised to type XII collagen synthesized in a bacterial expression system recognized not only previously reported bands (220 kD et cetera) in tendons, but also bands with apparently different molecular sizes in fibroblasts and 4-d embryos. The antibodies stained a wide variety of extracellular matrices in embryos in patterns distinct from those of fibronectin or interstitial collagens. They prominently stained extracellular matrix associated with certain neuronal tissues, such as axons from dorsal root ganglia and neural tube. These studies identify a novel chimeric type of molecule that contains both adhesion molecule and collagen motifs in one protein. Its structure blurs current classification schemes for extracellular proteins and underscores the potentially large diversity possible in these molecules.
细胞外基质分子通常分为胶原蛋白、弹性蛋白、蛋白聚糖或其他非胶原结构/细胞相互作用蛋白。这些细胞外蛋白中的许多都含有独特的重复模块，有时也能在其他蛋白中找到。我们描述了鸡胚成纤维细胞中 XII 型胶原蛋白α1 链的完整一级结构。通过 cDNA 分析鉴定出的这种大型结构嵌合分子，将先前不相关的分子结构域组合成一个由 3124 个残基组成的单一大型蛋白质（约 340 kD）。推导的鸡 XII 型胶原蛋白序列在氨基末端起始于一个纤连蛋白 III 型基序单元，接着是一个与血管性血友病因子 A 结构域同源的单元，然后是另一个纤连蛋白 III 型模块、第二个来自血管性血友病因子的 A 结构域、6 个 III 型基序单元和第三个 A 结构域、10 个连续的 III 型基序单元和第四个 A 结构域、一个与 IX 型胶原蛋白 NC4 结构域肽同源的结构域，最后是两个先前被描述为部分测序的 XII 型胶原蛋白分子一部分的短胶原区域；在一个胶原结构域末端的亲水区存在一个 Arg-Gly-Asp 潜在细胞黏附识别序列。在细菌表达系统中合成的针对 XII 型胶原蛋白的抗体，不仅能识别肌腱中先前报道的条带（220 kD 等），还能识别成纤维细胞和 4 天胚胎中分子大小明显不同的条带。这些抗体以与纤连蛋白或间质胶原蛋白不同的模式对胚胎中的多种细胞外基质进行染色。它们显著地对与某些神经组织相关的细胞外基质进行染色，如背根神经节和神经管的轴突。这些研究鉴定出一种新型的嵌合分子，该分子在一个蛋白质中同时包含黏附分子和胶原蛋白基序。其结构模糊了当前细胞外蛋白的分类方案，并强调了这些分子可能存在的巨大多样性。
