Extracellular matrix protein 1 interacts with the domain III of fibulin-1C and 1D variants through its central tandem repeat 2
Extracellular matrix protein 1 interacts with the domain III of fibulin-1C and 1D variants through its central tandem repeat 2
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DOI：
10.1016/j.bbrc.2005.06.046
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发表时间：
2005-08-12
影响因子：
3.1
通讯作者：
Uitto, J
中科院分区：
文献类型：
--
作者：
Fujimoto, N;Terlizzi, J;Uitto, J
细胞外基质蛋白1（ECM 1）是一种广泛表达的糖蛋白，已被证明在类脂质蛋白沉积症（LP）中存在突变，LP是一种常染色体隐性遗传疾病，其特征在于结缔组织细胞外基质的显著改变。ECM 1的生物学功能及其在LP病理机制中的作用尚不清楚。纤维蛋白包括细胞外基质组分的家族，并且该家族的原型，纤维蛋白-1，在各种结缔组织中表达并且在发育和病理过程中起作用。在这项研究中，我们表明，ECM 1，特别是第二串联重复结构域，这是选择性剪接，相互作用的C-末端片段的纤蛋白I C和I D剪接变体，不同的C-末端结构域III。通过酵母双杂交系统检测了它们之间的相互作用，并通过免疫共沉淀法进行了验证。通过生物传感器测定，ECM 1和fibulin-ID之间的结合动力学显示Kd为5.71 × 10（-8）M，表明蛋白质-蛋白质相互作用较强。由于不同的剪接变异体的ECM 1和fibulin-1已被证明是共同表达的组织中受影响的LP，我们建议，改变ECM 1/fibulin-1的相互作用可能在这种疾病的发病机制中发挥作用，以及在一些过程中涉及的细胞外基质的结缔组织。(c)2005年爱思唯尔公司All rights reserved.
Extracellular matrix protein 1 (ECM1), a widely expressed glycoprotein, has been shown to harbor mutations in lipoid proteinosis (LP), an autosomal recessive disorder characterized by profound alterations in the extracellular matrix of connective tissue. The biological function of ECM1 and its role in the pathomechanisms of LP are unknown. Fibulins comprise a family of extracellular matrix components, and the prototype of this family, fibulin-1, is expressed in various connective tissues and plays a role in developmental and pathologic processes. In this study, we demonstrate that ECM1, and specifically the second tandem repeat domain which is alternatively spliced, interacts with the C-terminal segments of fibulins I C and I D splice variants which differ in their C-terminal domain III. The interactions were detected by yeast two-hybrid genetic system and confirmed by co-immunoprecipitations. Kinetics of the binding between ECM1 and fibulin-ID, measured by biosensor assay, revealed a K-d of 5.71 x 10(-8) M, indicating a strong protein-protein interaction. Since distinct splice variants of ECM1 and fibulin-1 have been shown to be co-expressed in tissues affected in LP, we propose that altered ECM1/fibulin-1 interactions may play a role in the pathogenesis of this disease as well as in a number of processes involving the extracellular matrix of connective tissues. (c) 2005 Elsevier Inc. All rights reserved.