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首页> 外文期刊>Biochemistry >Interaction of recombinant subdomains of the procollagen C-proteinase with procollagen I provides a quantitative explanation for functional differences between the two splice variants, mammalian tolloid and bone morphogenetic protein 1
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Interaction of recombinant subdomains of the procollagen C-proteinase with procollagen I provides a quantitative explanation for functional differences between the two splice variants, mammalian tolloid and bone morphogenetic protein 1

机译：胶原蛋白C蛋白酶的重组子结构域与胶原蛋白I的相互作用为定量分析两种剪接变体，哺乳动物骨灰质和骨形态发生蛋白1之间的功能差异

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摘要

The procollagen C-proteinase (PCP) is a zinc peptidase of the astacin family and the metzincin superfamily. The enzyme removes the C-terminal propeptides of fibrillar procollagens and activates other matrix proteins. Besides its catalytic protease domain, the procollagen C-proteinase contains several C-terminal CUB modules (named after complement factors C1r and C1s, the sea urchin UEGF protein, and BMP-1) and EGF-like domains. The two major splice forms of the C-proteinase differ in their overall domain composition. The longer variant, termed mammalian tolloid (mTld, i.e., PCP-2), has the protease-CUB1- CUB2-EGF1-CUB3-EGF2-CUB4-CUB5 composition, whereas the shorter form termed bone morphogenetic protein 1 (BMP-1, i.e., PCP-1) ends after the CUB3 domain. Two related genes encode proteases similar to mTld in humans and have been termed mammalian tolloid like-1 and -2 (mTll-1 and mTll-2, respectively). For mTll-1, it has been shown that it has C-proteinase activity. We demonstrate that recombinant EGF1-CUB3,CUB3, CUB3-EGF2, EGF2-CUB4, and CUB4-CUB5 modules of the procollagen C-proteinase can be expressed in bacteria and adopt a functional antiparallel beta-sheet conformation. As shown by surface plasmon resonance analysis, the modules bind to procollagen I in a 1:1 stoichiometry with dissociation constants (K-D) ranging from 622.0 to 1.0 nM. Their binding to mature collagen I is weaker by at least 1 order of magnitude. Constructs containing EGF domains bind more strongly than those consisting of CUB domains only. This suggests that a combination of CUB and EGF domains serves as the minimal functional unit. The binding affinities of the EGF-containing modules for procollagen increase in the order EGF1-CUB3 < CUB3-EGF2 < EGF2-CUB4. In the context of the full length PCP, this implies that a given module has an affinity that continues to increase the more C-terminally the module is located within the PCP. The tightest binding module, EGF2-CUB4 (K-D = 1.0 nM), is only present in mTld, which might provide a quantitative explanation for the different efficiencies of BMP-1 and mTld in procollagen C-proteinase activity.
机译：前胶原C蛋白酶（PCP）是Astacin家族和metzincin超家族的锌肽酶。该酶去除了原纤维胶原的C末端前肽并激活了其他基质蛋白。除了其催化蛋白酶结构域外，前胶原C蛋白酶还包含几个C末端CUB模块（以补体因子C1r和C1s，海胆UEGF蛋白和BMP-1命名）和EGF样结构域。 C-蛋白酶的两个主要剪接形式在它们的整体结构域组成上不同。较长的变体称为哺乳动物类胚粉（mTld，即PCP-2），具有蛋白酶-CUB1-CUB2-EGF1-CUB3-EGF2-CUB4-CUB5组成，而较短的变体称为骨形态发生蛋白1（BMP-1，即PCP-1）在CUB3域之后结束。两种相关基因编码的人类蛋白酶与mTld相似，已被称为哺乳动物类Tolloid like-1和-2（分别为mTll-1和mTll-2）。对于mTll-1，已显示其具有C-蛋白酶活性。我们证明原胶原C蛋白酶的重组EGF1-CUB3，CUB3，CUB3-EGF2，EGF2-CUB4和CUB4-CUB5模块可以在细菌中表达并采用功能性反平行β-折叠构象。如表面等离子体共振分析所示，模块以1：1的化学计量比与原胶原I结合，解离常数（K-D）为622.0至1.0 nM。它们与成熟胶原蛋白I的结合至少弱1个数量级。包含EGF域的构建体比仅包含CUB域的构建体具有更强的结合力。这表明CUB和EGF结构域的组合充当最小功能单元。含EGF的模块对胶原蛋白的结合亲和力以EGF1-CUB3

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