Homologous Sequence in Lumican and Fibromodulin Leucine-rich Repeat 5-7 Competes for Collagen Binding
Homologous Sequence in Lumican and Fibromodulin Leucine-rich Repeat 5-7 Competes for Collagen Binding
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DOI：
10.1074/jbc.m805721200
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发表时间：
2009-01-02
影响因子：
4.8
通讯作者：
Oldberg, Ake
中科院分区：
文献类型：
--
作者：
Kalamajski, Sebastian;Oldberg, Ake
鲁米肯和纤维调素在体外竞争I型胶原结合，而纤维调素缺陷小鼠的肌腱中鲁米肯的数量是对照组的4倍。这些观察结果表明，LUMICAN和纤维调制素中的同源序列与I型胶原结合。在这里，我们证明LUMICAN与I型胶原的结合主要是通过富含亮氨酸的重复序列(LRR)7中的Asp-213介导的。LUMICAN中的突变D213N削弱了与胶原的相互作用，而LUMICA片段横跨LRRS5-7是一种有效的胶原结合抑制因子。此外，基于LUMICA LRR 7序列的合成肽CYLDNNKC抑制了与胶原的结合。位于LRRS5-7的纤维调素中的同源胶原结合部位抑制了鲁米肯与胶原的结合，而该纤维调素片段中的突变E251Q不抑制鲁米肯与胶原的结合。Lumcan，而不是D213N突变，降低了熔点，影响了胶原纤维的堆积。
Lumican and fibromodulin compete for collagen type I binding in vitro, and fibromodulin-deficient mice have 4-fold more lumican in tendons. These observations indicate that homologous sequences in lumican and fibromodulin bind to collagen type I. Here, we demonstrate that lumican binding to collagen type I is mediated mainly by Asp-213 in leucine-rich repeat ( LRR) 7. The mutation D213N in lumican impairs interaction with collagen, and the lumican fragment spanning LRRs 5-7 is an efficient inhibitor of collagen binding. Also, the lumican LRR 7 sequence-based synthetic peptide CYLDNNKC inhibits the binding to collagen. Homologous collagen-binding site in fibromodulin, located in LRRs 5-7, inhibits the binding of lumican to collagen, and the mutation E251Q in this fibromodulin fragment does not inhibit the lumican-collagen binding. Lumican, but not the D213N mutation, lowers the melting point and affects the packing of collagen fibrils.