Department of Biochemistry, Molecular Biology and Biotechnology, Faculty of Chemistry, Wrocław University of Science and Technology, Wrocław, Poland.
Faculty of Chemistry, University of Wrocław, Wrocław, Poland.
FASEB J. 2020 May;34(5):6147-6165. doi: 10.1096/fj.201901999R. Epub 2020 Mar 19.
Dentin matrix protein 1 (DMP1) is an acidic, extracellular matrix protein essential for biomineralization of calcium phosphate, in bone and dentin. It is proteolytically processed into two fragments, 44K and 56K. Recently, the presence of DMP1 was noticed in inner ear, specifically in otoconia, which are calcium carbonate biominerals involved in sensing of balance. In this study, the solution structure and biomineralization activity of otoconial 44K and 56K fragments toward calcium carbonate were investigated. The results of analytical ultracentrifugation, circular dichroism, and gel filtration indicated that DMP1 fragments are disordered in solution. Notably, 56K formed oligomers in the presence of calcium ions. It was also observed that both fragments influenced the crystal growth by in vitro biomineralization assay and scanning electron microscopy. In addition, they sequester the calcium ions during the calcite formation. Calcium carbonate crystals precipitated in vitro changed their size and shape in the presence of DMP1 fragments. Oligomerization propensity of 56K may significantly enhance this function. Our study indicates that intrinsically disordered DMP1 has a previously unknown regulatory function for biomineralization of otoconia.
牙本质基质蛋白 1（DMP1）是一种酸性细胞外基质蛋白，对于骨和牙本质中磷酸钙的生物矿化至关重要。它可被蛋白水解为两个片段，44K 和 56K。最近，人们注意到 DMP1 存在于内耳中，特别是在耳石中，耳石是参与平衡感的碳酸钙生物矿物质。在这项研究中，研究了耳石 44K 和 56K 片段对碳酸钙的溶液结构和生物矿化活性。分析超速离心、圆二色性和凝胶过滤的结果表明，DMP1 片段在溶液中是无规的。值得注意的是，56K 在钙离子存在下形成寡聚物。还观察到，这两个片段通过体外生物矿化实验和扫描电子显微镜影响晶体生长。此外，它们在方解石形成过程中螯合钙离子。体外沉淀的碳酸钙晶体在 DMP1 片段存在下改变了其大小和形状。56K 的寡聚倾向可能会显著增强这种功能。我们的研究表明，固有无序的 DMP1 对耳石的生物矿化具有以前未知的调节功能。
