Heterotrimeric type I collagen C-telopeptide conformation as docked to its helix receptor.
Heterotrimeric type I collagen C-telopeptide conformation as docked to its helix receptor.
复制标题
异源三聚体 I 型胶原 C 端肽构象与其螺旋受体对接。
DOI：
10.1021/bi048304b
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Veis,Arthur
中科院分区：
文献类型：
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作者：
Malone,JamesP;Veis,Arthur
I型胶原的氨基端肽（N-telo）和羧基端肽（C-telo）在体内和体外胶原原纤维的组装中起着至关重要的作用，调节原纤维内分子的轴向排列、相邻分子的方位角取向和交联形成。端肽的高分辨率结构不能从X-射线衍射研究中获得，但计算方法允许预测原纤维内的N-端肽结构。在这里，使用一套分子建模软件，更复杂的异源三聚体的人I型胶原蛋白的C-末端已建立从正确的序列和能量最小化，并通过分子动力学确认的能量最小值。受体三螺旋是基于胶原蛋白样序列的蛋白质数据库坐标建模的。异源三聚体C端肽与其受体的对接表明，涉及短α2 C端肽的疏水相互作用是其在对接结构内方位角取向的关键决定因素。一个停靠的C-telo只能与一个相邻的螺旋相互作用。在α1（A）-α2-α1（B）链交错中的两条α1（I）C-telo链没有相同的对接构象，其中一条α1（I）C-telo链似乎有利于在其K16 C和螺旋K87之间形成交联。先前的研究表明，对接的N-端肽可以与两个相邻的胶原蛋白单体相互作用，形成紧密堆积的区域。最近的X射线分析显示，N-和C-telo区域的包装不同，C-telo区域的包装密度低于N-telo区域。N-和C-端肽对接结构之间的这种差异证明了在I型胶原间隙区域的每个边界处的原纤维中如何发生独特和特异性的包装。
The amino (N-telo) and carboxyl (C-telo) telopeptides of type I collagen play crucial roles,in vivoandin vitro, in the assembly of collagen fibrils, regulating the axial alignment of the molecules within a fibril, azimuthal orientations of neighboring molecules, and cross-link formation. High-resolution structures of the telopeptides are not available from X-ray diffraction studies, but computational methods permitted prediction of the N-telo structure within a fibril. Here, using a suite of molecular modeling software, the more complex heterotrimeric C-telo of human type I collagen has been built from the correct sequences and energy minimized and the energy minimum confirmed by molecular dynamics. The receptor triple helix was modeled on the basis of the Protein Data Bank coordinates of a collagen-like sequence. Docking of the heterotrimeric C-telopeptide to its receptor showed that hydrophobic interactions involving the short α2 C-telopeptide are crucial determinants of its azimuthal orientation within the docked structure. A docked C-telo can interact with only one neighboring helix. The two α1(I) C-telo chains in the α1(Α)−α2−α1(Β) chain stagger do not have identical docked conformations, and one of the α1(I) C-telo chains appears to be favored for formation of a cross-link between its K16Cand a helix K87. Prior studies showed that a docked N-telopeptide can interact with two adjacent collagen monomers, forming a tightly packed region. A recent X-ray analysis showed the N- and C-telo regions pack differently, with the C-telo region being less densely packed than N-telo regions. This difference between N- and C-telopeptide docked structures demonstrates how unique and specific packing can occur in the fibril at each boundary of the type I collagen gap region.