Fibromodulin Interacts with Collagen Cross-linking Sites and Activates Lysyl Oxidase.
Fibromodulin Interacts with Collagen Cross-linking Sites and Activates Lysyl Oxidase.
复制标题
纤维瘤蛋白与胶原蛋白交联位点相互作用，并激活赖氨酸氧化酶。
DOI：
10.1074/jbc.m115.693408
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发表时间：
2016-04-08
期刊：
影响因子：
--
通讯作者：
Farndale RW
中科院分区：
文献类型：
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作者：
Kalamajski S;Bihan D;Bonna A;Rubin K;Farndale RW
纤维化疾病的标志是高度交联和致密的胶原基质，这是赖氨酰氧化酶的氧化作用驱动的性质。其他纤维化相关蛋白也有助于最终的胶原基质性质，其中之一是纤调蛋白。它与胶原蛋白的相互作用影响胶原蛋白的交联、堆积和原纤维直径。我们研究了纤调蛋白和赖氨酰氧化酶之间存在特定关系的可能性，可能赋予特定的胶原基质表型。我们使用胶原蛋白II和III工具包肽库绘制了纤调蛋白-胶原蛋白相互作用位点。纤调蛋白与含有胶原蛋白I和II中的已知胶原交联位点和MMP-1裂解位点的肽相互作用。有趣的是，相互作用的网站是紧密对齐的四分之一交错的胶原纤维，这表明纤调蛋白和几个胶原螺旋之间的多价相互作用。此外，我们检测到纤调蛋白和赖氨酰氧化酶（一种主要的胶原交联酶）之间的相互作用，并映射到纤调蛋白上的12个N-末端氨基酸的相互作用位点。这种相互作用还增加了赖氨酰氧化酶的活性。总之，这些数据表明纤调蛋白调节的胶原交联机制，其中纤调蛋白与胶原结构域的特定部分结合，并且还与赖氨酰氧化酶形成复合物，将酶靶向特定的交联位点。
The hallmark of fibrotic disorders is a highly cross-linked and dense collagen matrix, a property driven by the oxidative action of lysyl oxidase. Other fibrosis-associated proteins also contribute to the final collagen matrix properties, one of which is fibromodulin. Its interactions with collagen affect collagen cross-linking, packing, and fibril diameter. We investigated the possibility that a specific relationship exists between fibromodulin and lysyl oxidase, potentially imparting a specific collagen matrix phenotype. We mapped the fibromodulin-collagen interaction sites using the collagen II and III Toolkit peptide libraries. Fibromodulin interacted with the peptides containing the known collagen cross-linking sites and the MMP-1 cleavage site in collagens I and II. Interestingly, the interaction sites are closely aligned within the quarter-staggered collagen fibril, suggesting a multivalent interaction between fibromodulin and several collagen helices. Furthermore, we detected an interaction between fibromodulin and lysyl oxidase (a major collagen cross-linking enzyme) and mapped the interaction site to 12 N-terminal amino acids on fibromodulin. This interaction also increases the activity of lysyl oxidase. Together, the data suggest a fibromodulin-modulated collagen cross-linking mechanism where fibromodulin binds to a specific part of the collagen domain and also forms a complex with lysyl oxidase, targeting the enzyme toward specific cross-linking sites.