Crystal structure of human bone morphogenetic protein-2 at 2.7 Å resolution
Crystal structure of human bone morphogenetic protein-2 at 2.7 Å resolution
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DOI：
10.1006/jmbi.1999.2590
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发表时间：
1999-03-19
影响因子：
5.6
通讯作者：
Hülsmeyer, M
中科院分区：
文献类型：
--
作者：
Scheufler, C;Sebald, W;Hülsmeyer, M
同二聚体骨形态发生蛋白-2 (BMP-2) 是转化生长因子β (TGF-β) 超家族的成员，可诱导骨形成和再生，并决定脊椎动物和非脊椎动物胚胎发育早期阶段的重要步骤。 BMP-2 可以与两种类型的受体链以及细胞外基质蛋白和多种调节蛋白相互作用。我们在这里报告了通过分子置换确定的人类 BMP-2 的晶体结构，并在 2.7 埃分辨率下精修至 R 值 24.2%。 BMP-2、BMP-7 和 TGP-β 的共同支架，即胱氨酸结基序和两个指状双链 β 片层，可以与均方根叠加。偏差约为 1 埃。与 TGF-β 相比，BMP-2 的结构在 N 末端的灵活性和中央 a 螺旋的方向以及指尖处的两个外部环相对于支架表现出差异。从BMP-7型号中也可以得知这一点。 BMP-2 和 BMP-7 环区域中的小二级结构元件似乎对于各自的 BMP 亚组是特定的。位于二聚体中心二倍轴周围的两个相同的螺旋指裂缝和两个不同的空腔显示出特征形状、极性和表面电荷。讨论了这些特定特征在 BMP-2 与其结合配偶体相互作用中的可能功能。 (C) 1999 年学术出版社。
Homodimeric bone morphogenetic protein-2 (BMP-2) is a member of the transforming growth factor beta (TGF-beta) superfamily that induces bone formation and regeneration, and determines important steps during early stages of embryonic development in vertebrates and non-vertebrates. BMP-2 can interact with two types of receptor chains, as well as with proteins of the extracellular matrix and several regulatory proteins. We report here the crystal structure of human BMP-2 determined by molecular replacement and refined to an R-value of 24.2% at 2.7 Angstrom resolution. A common scaffold of BMP-2, BMP-7 and the TGP-beta s, i.e. the cystine-knot motif and two finger-like double-stranded beta-sheets, can be superimposed with r.m.s. deviations of around 1 Angstrom. In contrast to the TGF-beta s, the structure of BMP-2 shows differences in the flexibility of the N terminus and the orientation of the central a-helix as well as two external loops at the fingertips with respect to the scaffold. This is also known from the BMP-7 model. Small secondary structure elements in the loop regions of BMP-2 and BMP-7 seem to be specific for the respective BMP-subgroup. Two identical helix-finger clefts and two distinct cavities located around the central 2-fold axis of the dimer show characteristic shapes, polarity and surface charges. The possible function of these specific features in the interaction of BMP-2 with its binding partners is discussed. (C) 1999 Academic Press.