POSTTRANSLATIONAL PROCESSING OF PROCOLLAGENS
POSTTRANSLATIONAL PROCESSING OF PROCOLLAGENS
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DOI：
10.1111/j.1749-6632.1985.tb51167.x
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发表时间：
1985-12-30
影响因子：
5.2
通讯作者：
MYLLYLA, R
中科院分区：
文献类型：
--
作者：
KIVIRIKKO, KI;MYLLYLA, R
胶原蛋白生物合成的特征在于存在异常大量的共翻译和翻译后修饰，其中许多是胶原蛋白和一些具有胶原蛋白样氨基酸序列的其他蛋白质所特有的。前胶原的翻译后加工可分为两个阶段（图1）。细胞内修饰与多肽链的合成一起导致三螺旋前胶原分子的形成，然后细胞外加工将这些分子转化为胶原并将其掺入稳定的交联原纤维或其他超分子结构中。表1中总结了主要修饰及其生物学功能。前胶原的翻译后加工需要至少九种特异性酶和几种非特异性酶。大多数特异性酶现已被纯化和表征（表Z），反应的基本特征也已明确。在一种酶的情况下，前胶原NH-末端蛋白酶，一种特异于I型和I1型前胶原的同工酶和一种特异于I11型前胶原的第二同工酶已被鉴定，而在其他翻译后反应中，相同的酶似乎处理许多不同的前胶原类型。几乎所有的特定加工事件都表现出与被修饰蛋白质构象的不寻常关系。前α链必须是非螺旋的，以便作为五种细胞内酶的底物，即三种胶原羟化酶和两种将糖加到羟赖氨酸残基上的转移酶（图1）。一旦蛋白质折叠成三螺旋，所有这些酶的修饰就会停止，并且折叠实际上限制了特定细胞内翻译后修饰可以进行的程度。一旦折叠，前胶原被分泌，折叠所需的时间直接影响分泌所需的时间。大多数胞外酶对底物的构象也有严格的要求。前胶原NH-末端蛋白酶仅在相应的蛋白质折叠成三螺旋时才切割它们，赖氨酰氧化酶仅在胶原蛋白并入天然型原纤维后才作用于胶原蛋白（参见下文所述的综述）。这篇文章将主要集中在最新的发现，读者可以参考关于这些修饰的各个方面和一般胶原蛋白生物合成的最新评论，以获得更详细的参考资料。或细胞内修饰，8.羟基化、”糖基化“、”细胞外修饰”、赖氨酰氧化酶、I3和交联形成。L~
Collagen biosynthesis is characterized by the presence of an unusually large number of cotranslational and post-translational modifications, many of which are unique to collagens and a few other proteins with collagen-like amino acid sequences. The posttranslational processing of procollagens can be regarded as occurring in two stages (FIGURE 1). Intracellular modifications, together with synthesis of the polypeptide chains, result in the formation of triple-helical procollagen molecules, and extracellular processing then converts these molecules into collagens and incorporates them into stable, cross-linked fibrils or other supramolecular structures. The main modifications and their biological functions are summarized in TABLE 1. The post-translational processing of procollagens requires at least nine specific enzymes and several nonspecific ones. Most of the specific enzymes have now been purified and characterized (TABLE Z), and the basic features of the reactions are also well defined. In the case of one of the enzymes, procollagen NH,-terminal proteinase, an isozyme specific for type I and type I1 procollagen and a second isozyme specific for type I11 procollagen have been identified, whereas in the other post-translational reactions the same enzymes appear to process many different procollagen types. Almost all the specific processing events demonstrate an unusual relationship to the conformation of the protein being modified. The pro-a chains must be nonhelical in order to serve as substrates for the five intracellular enzymes, ie, the three collagen hydroxylases and the two transferases which add sugars to the hydroxylysine residues (FIGURE 1). Once the protein folds into the triple helix, modification by all these enzymes ceases, and the folding in fact limits the extent to which the specific intracellular post-translational modifications can proceed. Once folded, the procollagen is secreted, and the time required for folding directly affects that required for secretion. Most of the extracellular enzymes also show strict requirements concerning the conformation of their substrates. Procollagen NH,-terminal proteinases cleave the corresponding proteins only if they are folded into the triple helix, and lysyl oxidase will act on collagen only after it has become incorporated into native-type fibrils (see reviews mentioned below).The literature on collagen post-translational processing is now voluminous. This article will concentrate mainly on the most recent discoveries, and the reader is referred for more detailed references to recent reviews on various aspects of these modifications and on collagen biosynthesis in general,'.'or on the intracellular modifi~ ations, 8.~ hydroxylations," glycosylations," extracellular modifications," lysyl oxidase, I3 and cross-link f0rmati0n. l~