Bioinformatic analysis and molecular modelling of human ameloblastin suggest a two-domain intrinsically unstructured calcium-binding protein
Bioinformatic analysis and molecular modelling of human ameloblastin suggest a two-domain intrinsically unstructured calcium-binding protein
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DOI：
10.1111/j.1600-0722.2008.00526.x
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发表时间：
2008-04-01
影响因子：
1.9
通讯作者：
Lyngstadaas, S. Petter
中科院分区：
文献类型：
--
作者：
Vymetal, Jiri;Slaby, Ivan;Lyngstadaas, S. Petter
成釉细胞（AMBN）最初被认为是由成釉细胞分泌的釉质特异性细胞外基质糖蛋白。最近，在发育中的间充质牙齿硬组织、创伤引起的修复性牙本质以及早期颅面骨形成过程中也检测到了 AMBN 表达。 AMBN 的功能和结构仍然不明确，并且没有已知的具有相似一级序列的蛋白质。因此，我们对 AMBN 进行了生物信息学分析，从头开始模拟分子的三维结构。结果表明 AMBN 是一种具有两个结构域的本质上非结构蛋白 (IUP)。该分析没有揭示任何与已知受体-配体系统结构相似的区域，也没有识别出任何与其他已知序列中的功能区域相似的高级结构。 AMBN 模型预测表面暴露的 11 个定义区域，内化分子的其余部分，包括人类特异性插入物。分子动力学分析确定了一个特定的和几个非特定的钙结合区域，主要位于分子的 C 末端部分。该模型得到了先前观察结果的支持，即 AMBN 是一种双极钙结合分子，并暗示其在蛋白质-蛋白质相互作用中可能发挥作用。该模型为进一步研究 AMBN 的功能提供了有用的信息。
Ameloblastin (AMBN) was originally believed to be an enamel-specific extracellular matrix glycoprotein secreted by ameloblasts. Recently, AMBN expression was also detected in developing mesenchymal dental hard tissues, in trauma-induced reparative dentin, and during early craniofacial bone formation. The function and structure of AMBN still remain ambiguous, and there are no known proteins with similar primary sequences. We therefore performed a bio-informatic analysis of AMBN to model ab initio the three-dimensional structure of the molecule. The results suggest that AMBN is a two-domain, intrinsically unstructured protein (IUP). The analysis did not reveal any regions with structural similarity to known receptor-ligand systems, and did not identify any higher-order structures similar to functional regions in other known sequences. The AMBN model predicts 11 defined regions exposed on the surface, internalizing the rest of the molecule including a human-specific insert. Molecular dynamics analysis identified one specific and several non-specific calcium-binding regions, mostly at the C-terminal part of the molecule. The model is supported by previous observations that AMBN is a bipolar calcium-binding molecule and hints at a possible role in protein-protein interactions. The model provides information useful for further studies on the function of AMBN.