Molecules in Focus: Collagen XII: Protecting bone and muscle integrity by organizing collagen fibrils
Molecules in Focus: Collagen XII: Protecting bone and muscle integrity by organizing collagen fibrils
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发表时间：
2014
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通讯作者：
M. Chiquet;D. Birk;C. Bönnemann;M. Koch
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作者：
M. Chiquet;D. Birk;C. Bönnemann;M. Koch
XII 胶原蛋白是具有间断三螺旋 (FACIT) 家族的原纤维相关胶原蛋白 (FACIT) 家族中最大的成员，由 COL12A1 基因编码的三个相同的 α 链组装而成。该分子由三个线状 N 端非胶原 NC3 结构域组成，通过二硫键和朝向 C 端的短中断胶原三螺旋连接。剪接变体在大小和特性上有很大差异：“小”胶原蛋白 XIIB（220 kDa 亚基）与胶原蛋白 XIV 相似，而胶原蛋白 XIIA（350 kDa）具有更大的携带糖胺聚糖链的 NC3 结构域。 XII 胶原蛋白通过其胶原结构域与含有胶原蛋白 I 的原纤维结合，而其大的非胶原臂与其他基质蛋白（如腱蛋白-X）相互作用。在致密结缔组织和骨骼中，XII 胶原蛋白被认为可以调节胶原原纤维束的组织和机械性能。因此，最近的研究结果表明，XII 型胶原蛋白突变会导致与小鼠和人类骨骼异常和肌肉无力相关的 Ehlers-Danlos/肌病重叠综合征。
Collagen XII, largest member of the fibril-associated collagens with interrupted triple helix (FACIT) family, assembles from three identical α -chains encoded by the COL12A1 gene. The molecule consists of three threadlike N-terminal noncollagenous NC3 domains, joined by disulfide bonds and a short interrupted collagen triple helix towards the C-terminus. Splice variants differ considerably in size and properties: "small" collagen XIIB (220 kDa subunit) is similar to collagen XIV, whereas collagen XIIA (350 kDa) has a much larger NC3 domain carrying glycosaminoglycan chains. Collagen XII binds to collagen I-containing fibrils via its collagenous domain, whereas its large noncollagenous arms interact with other matrix proteins such as tenascin-X. In dense connective tissues and bone, collagen XII is thought to regulate organization and mechanical properties of collagen fibril bundles. Accordingly, recent findings show that collagen XII mutations cause Ehlers-Danlos/myopathy overlap syndrome associated with skeletal abnormalities and muscle weakness in mice and humans.