A N-Terminus Domain Determines Amelogenin's Stability to Guide the Development of Mouse Enamel Matrix.
A N-Terminus Domain Determines Amelogenin's Stability to Guide the Development of Mouse Enamel Matrix.
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N-末端结构域决定釉原蛋白的稳定性以指导小鼠牙釉质基质的形成
DOI：
10.1002/jbmr.4329
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发表时间：
2021-09
影响因子：
6.2
通讯作者：
Zhang, Yan
中科院分区：
文献类型：
--
作者：
Huang, Yulei;Bai, Yushi;Chang, Chih;Bacino, Margot;Cheng, Ieong Cheng;Li, Li;Habelitz, Stefan;Li, Wu;Zhang, Yan
釉原蛋白是发育中的釉质微环境中的主要蛋白质，它们自组装成超分子结构，以控制蛋白质有机基质重塑为纵向有序的羟基磷灰石纳米晶体阵列。利用纯化的天然或重组蛋白质进行的大量体外研究揭示了N -末端釉原蛋白在蛋白质自组装方面的潜力及其引导矿物质沉积的能力。我们先前已经确定了N -末端釉原蛋白的一个14个氨基酸的结构域（P2），它在体外能够自组装成淀粉样纤维。在这里，我们在一个体内动物模型中研究了这个结构域如何影响釉原蛋白自组装的能力以及釉质基质蛋白支架的稳定性。携带缺失P2结构域的突变釉原蛋白的小鼠具有发育不全、矿化不足和无棱柱的釉质。在体外，缺失P2的突变重组釉原蛋白自组装的趋势降低，并且容易被MMP20（早期发育的釉质基质中主要的金属蛋白酶）加速水解。与野生型小鼠釉质基质相比，突变小鼠发育中的釉质基质中釉原蛋白的量减少，并且缺乏细长的纤维状聚集体。我们的研究首次证明，釉原蛋白N -末端的一个亚结构域（P2）控制釉原蛋白组装成一个在动物模型中釉质发育过程中抵抗快速蛋白水解的瞬时蛋白质支架。了解引导釉质基质中羟基磷灰石纵向生长的纤维支架的组成部分，为蛋白质介导的釉质生物工程提供了启示。
Amelogenins, the principal proteins in the developing enamel microenvironment, self-assemble into supramolecular structures to govern the remodeling of a proteinaceous organic matrix into longitudinally ordered hydroxyapatite nanocrystal arrays. Extensive in vitro studies using purified native or recombinant proteins have revealed the potential of N-terminal amelogenin on protein self-assembly and its ability to guide the mineral deposition. We have previously identified a 14-aa domain (P2) of N-terminal amelogenin that can self-assemble into amyloid-like fibrils in vitro. Here we investigated how this domain affects the ability of amelogenin self-assembling and stability of enamel matrix protein scaffolding in an in vivo animal model. Mice harboring mutant amelogenin lacking P2 domain had a hypoplastic, hypomineralized and aprismatic enamel. In vitro, the mutant recombinant amelogenin without P2 had a reduced tendency to self-assemble and was prone to accelerated hydrolysis by MMP20, the prevailing metalloproteinase in early developing enamel matrix. A reduced amount of amelogenins and a lack of elongated fibrous assemblies in the development enamel matrix of mutant mice were evident as compared to that in the wild type mouse enamel matrix. Our study is the first to demonstrate that a subdomain (P2) at the N-terminus of amelogenin controls amelogenin’s assembly into a transient protein scaffold that resists rapid proteolysis during enamel development in an animal model. Understanding the building blocks of fibrous scaffold that guides the longitudinal growth of hydroxyapatites in enamel matrix sheds light on protein-mediated enamel bioengineering.
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影响因子：
4.6
作者：
Carneiro KM;Zhai H;Zhu L;Horst JA;Sitlin M;Nguyen M;Wagner M;Simpliciano C;Milder M;Chen CL;Ashby P;Bonde J;Li W;Habelitz S
通讯作者：
Habelitz S
影响因子：
3
作者：
Fang, Ping-An;Margolis, Henry C.;Conway, James F.;Simmer, James P.;Beniash, Elia
通讯作者：
Beniash, Elia
DOI：
10.1073/pnas.0638023100
发表时间：
2003-04-01
影响因子：
11.1
作者：
Kawasaki, K;Weiss, KM
通讯作者：
Weiss, KM
影响因子：
4.8
作者：
Bromley, Keith M.;Kiss, Andrew S.;Moradian-Oldak, Janet
通讯作者：
Moradian-Oldak, Janet
影响因子：
4.2
作者：
AOBA, T;FUKAE, M;MORENO, EC
通讯作者：
MORENO, EC