Unraveling the mechanism for an amelogenin-derived peptide regulated hydroxyapatite mineralization via specific functional domain identification
Unraveling the mechanism for an amelogenin-derived peptide regulated hydroxyapatite mineralization via specific functional domain identification
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DOI：
10.1039/d0tb00949k
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发表时间：
2020-12-07
影响因子：
7
通讯作者：
Zhang，Linglin
中科院分区：
文献类型：
--
作者：
Wang，Yufei;Hu，Die;Zhang，Linglin
釉原蛋白及其衍生肽在促进釉质仿生矿化中发挥重要作用。此前，一种名为QP 5的釉原蛋白衍生肽被证明能够修复脱矿牙釉质。本文的目的是通过阐明QP 5每个结构域的具体功能来解释QP 5的机制，以进一步序列和功效改进。将肽QP 5分成结构域（QPX）5和C-尾。还合成了（QPX）3以研究QPX重复如何影响矿化过程。圆二色谱分析表明，两个（QPX）重复序列为β折叠结构，而C尾为无序结构。在激光共聚焦显微镜观察中，（QPX）5比C-尾有更大的吸收，在Langmuir吸附等温线上有更高的K值，而亲水性更好的（QPX）3比（QPX）5有更大的吸附能力。钙消耗动力学、透射电镜和选区电子衍射结果表明，（QPX）5、C-tail和（QPX）3对自发钙消耗的抑制作用相似，成核产物的形貌相似，而QP 5的抑制作用更强，诱导了拉长的板状晶体。X射线衍射分析表明，C-尾和（QPX）3均具有较大的提高磷灰石晶体取向度的潜力。结果表明，（QPX）5是HAP的主要吸附区域，（QPX）5和C-尾都抑制了HAP的成核，且C-尾对提高HAP的取向度贡献更大，因此QP 5可以起到明显的非均化作用。通过减少两个重复序列，（QPX）3比（QPX）5表现出更高的疏水性和更高的结合亲和力，在提高HAP取向度方面具有更大的潜力和更低的经济成本。
Amelogenin and its various derived peptides play important roles in promoting biomimetic mineralization of enamel. Previously, an amelogenin-derived peptide named QP5 was proved to be able to repair demineralized enamel. The objective here was to interpret the mechanism of QP5 by elucidating the specific function of each domain for further sequence and efficacy improvement. Peptide QP5 was separated into domains (QPX)5 and C-tail. (QPX)3 was also synthesized to investigate how QPX repeats affect the mineralization process. Circular dichroism spectroscopy showed that two (QPX) repeats adopted a β-sheet structure, while C-tail exhibited a disordered structure. (QPX)5 showed more absorption in confocal laser scanning microscopy observation and a higher K value in Langmuir adsorption isotherms compared to C-tail, while (QPX)3 with better hydropathy had greater adsorption capability than (QPX)5. Meanwhile, calcium consumption kinetics, transmission electron microscopy and selected area electron diffraction indicated that (QPX)5, C-tail and (QPX)3 had similar inhibitory effects on the spontaneous calcium consumption and the morphology of their nucleation products were alike, while QP5 had a greater inhibitory effect than them and induced elongated plate-like crystals. X-Ray diffraction further showed that both C-tail and (QPX)3 had greater potential in improving the apatite crystal orientation degree. In conclusion, (QPX)5 was the major adsorption region, both (QPX)5 and C-tail inhibited the nucleation, and C-tail contributed more to improve the HAP orientation degree, so QP5 could exert a significant remineralization effect. By reducing two repeats, (QPX)3 showed higher hydropathicity than (QPX)5 and achieved higher binding affinity, and it was more potential in improving the HAP orientation degree with lower economic cost.