Structure and function of ameloblastin as an extracellular matrix protein: adhesion, calcium binding, and CD63 interaction in human and mouse.

Structure and function of ameloblastin as an extracellular matrix protein: adhesion, calcium binding, and CD63 interaction in human and mouse.
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DOI:
10.1111/j.1600-0722.2011.00889.x
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发表时间:
2011-12
影响因子:
1.9
通讯作者:
Luan X
Luan X
中科院分区:
医学4区
文献类型:
--
作者:
Zhang X;Diekwisch TG;Luan X

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细胞外基质蛋白在脊椎动物生命中的功能意义是由高水平的序列变异性与细胞-细胞和细胞-基质粘附相互作用方面的相当程度的保守性串联而强调的。许多细胞外基质蛋白具有多个粘附结构域,用于成功地附着于底物,如整合素、CD 63和肝素。在这里,我们使用同源性和从头建模算法比较小鼠(mAMBN)和人成釉蛋白(hABMN)亚型,并分析其与其他基质分子的细胞粘附和相互作用以及钙结合的潜力。mAMBN和hAMBN之间的序列比较揭示了mAMBN中26个氨基酸的缺失,对应于螺旋-环-螺旋移码。与mAMBN 157 E-178 I螺旋-环-螺旋区同源的人AMBN结构域(174 Q-201 G)形成了具有延伸环的螺旋/环基序,表明hAMBN的灵活性高于mAMBN,如分子动力学模拟所证实的。肝素结合结构域,CD 63相互作用结构域,和钙结合位点的hAMBN和mAMBN支持的概念AMBN作为细胞外基质蛋白。与仅61%的氨基酸序列同源性相比,与粘附和分化相关的AMBN功能结构域之间的高水平保守性是显著的。
The functional significance of extracellular matrix proteins in the life of vertebrates is underscored by a high level of sequence variability in tandem with a substantial degree of conservation in terms of cell-cell and cell-matrix adhesion interactions. Many extracellular matrix proteins feature multiple adhesion domains for successful attachment to substrates, such as integrin, CD63, and heparin. Here we have used homology and ab initio modeling algorithms to compare mouse (mAMBN) and human ameloblastin (hABMN) isoforms and to analyze their potential for cell adhesion and interaction with other matrix molecules as well as calcium binding. Sequence comparison between mAMBN and hAMBN revealed a 26 amino acid deletion in mAMBN, corresponding to a helix-loop-helix frameshift. The human AMBN domain (174Q-201G) homologous to the mAMBN 157E-178I helix-loop-helix region formed a helix/loop motif with an extended loop, suggesting a higher degree of flexibility of the hAMBN compared to mAMBN, as confirmed by Molecular Dynamics simulation. Heparin binding domains, CD63 interaction domains, and calcium binding sites in both hAMBN and mAMBN support the concept of AMBN as an extracellular matrix protein. The high level of conservation between AMBN functional domains related to adhesion and differentiation was remarkable when compared to only 61% amino acid sequence homology.
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