【8.3.3】胶原蛋白

胶原蛋白作为动物细胞胞外基质内的一种主要结构蛋白，广泛存在于动物的结缔组织和其他纤维样组织中，如肌腱、韧带、骨骼和血管，是哺乳动物体内含量最丰富的蛋白质。食品工业上经常使用的明胶（gelatin）就是动物胶原蛋白经酸或碱部分水解的产物。

1. 人体内含量最丰富的蛋白质和构成结缔组织，如肌腱、软骨、骨骼和牙齿 的主要成分(The most abundant protein in our body and principal component of connective tissue (tendons, cartilage, bones, teeth)
2. 含有3条缠绕在一起的多肽链(composed of three intertwined polypeptide chains)
3. 一级结构:重复的三元体序列(Gly-X-Y)n，X和Y 通常是Pro和Lys，而Pro 和Lys经常发生了羟基化修饰(Primary structure: (Gly-X-Y)n, Nearly one residue out of three is Gly, X and Y are usually Proline and lysine. Unusual amino acids found: hydroxyproline and hydroxylysine)
4. 二级结构:大量Pro的存在使其无法形成α螺旋和β折叠，但却适合形成一 种它特有的二级结构——三股螺旋(Second structure: The unusual amino acid composition of collagen is unsuited for alpha helices OR beta sheets. But it is ideally suited for the collagen triple helix: three intertwined helical strands)

胶原蛋白的三股螺旋(The collagen triple helix)

1. 由3条肽链组成，每一条链折叠成左手螺旋。3条肽链形成的左手 螺旋在缠绕在一起，形成右手三股螺旋(it is made up of three polypeptide strands , each possessing the conformation of a left-handed helix. These three left-handed helices are twisted together into a right- handed triple helix).
2. 每隔3个残基面向螺旋拥挤的中央，Gly正适合这样的位置。让Gly 发生取代的突变可导致缺陷的结构分子，进而导致成骨不全症 (Every third residue faces the crowded center of the helix - only Gly fits here. Mutation that causes replacement of Gly leads to defective molecules and Osteogenesis Imperfecta).
3. 链之间的氢键稳定螺旋的结构(Interchain H-bonds involving HyP stabilize helix).
4. 胶原蛋白形成的纤维还可以借助链内和链之间的共价交联而得以 加固(Fibrils are further strengthened by intrachain lysine-lysine and interchain hydroxypyridinium crosslinks).

为什么需要对Pro和Lys进行羟基化 (Why has to hydroxylate Pro or Lys)?

答案是引入额外的氢键供体，以稳定三股螺旋结构，因为Pro为亚氨基酸(The answer: Introduce extra hydrogen bond donors -OH to stabilize the triple helix)

羟基化修饰需要羟化酶，而此酶需要维生素C，缺乏维生素C会导致酶活性中心的二 价铁易氧化失活，从而导致坏血病(The modifications are catalyzed by hydroxylase. The hydroylation vitamin C. and is activated by Fe 2+. Vitamin C helps to keep iron in the ferrous state, so its deficiency can cause Scurvy).

胶原蛋白上面的共价交联(Covalent crosslinks on the collagen molecules)

Lys-lys之间的交联和Met-Hyl之间的硫亚胺交联 (Lys-lys cross-links or Met-Hyl-sulfilimine links).

溴是组织发育和结构形成中胶原蛋白质IV组装必需的微量元素(Bromine Is an Essential Trace Element for Assembly of Collagen IV Scaffolds in Tissue Development and Architecture :Cell 157, 1380–1392, June 5, 2014 )

参考资料

• 南京大学 杨荣武老师 《结构生物学》课件