Microfibrillar structure of type I collagen in situ
Microfibrillar structure of type I collagen in situ
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DOI：
10.1073/pnas.0502718103
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发表时间：
2006-06-13
影响因子：
11.1
通讯作者：
Wess, Tim J.
中科院分区：
文献类型：
--
作者：
Orgel, Joseph P. R. O.;Irving, Thomas C.;Wess, Tim J.
纤维胶原在动物中普遍存在，并形成所有哺乳动物结缔组织的结构基础，包括心脏、脉管系统、皮肤、角膜、骨和肌腱的结缔组织。然而，与已知的它们的生产、周转和生理结构相比，关于胶原分子在天然存在的原纤维中的三维排列的了解很少。这些知识可以提供对关键生物过程的洞察，如纤维形成和组织重塑，以及心脏病和癌症等疾病。在这里，我们提出了一个晶体测定胶原蛋白I型超分子结构，其中每个胶原蛋白段的分子构象内发现的自然发生的晶体晶胞已被定义（P1，a约为40.0埃，B约为27.0埃，c约为678埃，α约为89.2度，ss约为94.6度，伽马105.6度;反射：414，重叠，232，和非重叠，182;分辨率，5.16埃轴向和11.1埃赤道）。该结构表明胶原分子的分子堆积拓扑结构是这样的，即堆积邻居被排列以形成与相邻微纤维交错的超扭曲（不连续）右手微纤维。这种交错建立了晶体学超晶格，它是由准六边形包装的胶原分子形成的。此外，这里显示的胶原蛋白的分子堆积结构提供了关于涉及人类健康和疾病的两种主要分子的潜在作用模式的信息：核心蛋白聚糖和基质金属蛋白酶（MMP）胶原酶。
The fibrous collagens are ubiquitous in animals and form the structural basis of all mammalian connective tissues, including those of the heart, vasculature, skin, cornea, bones, and tendons. However, in comparison with what is known of their production, turnover and physiological structure, very little is understood regarding the three-dimensional arrangement of collagen molecules in naturally occurring fibrils. This knowledge may provide insight into key biological processes such as fibrillo-genesis and tissue remodeling and into diseases such as heart disease and cancer. Here we present a crystallographic determination of the collagen type I supermolecular structure, where the molecular conformation of each collagen segment found within the naturally occurring crystallographic unit cell has been defined (P1, a approximate to 40.0 angstrom, b approximate to 27.0 angstrom, c approximate to 678 angstrom, alpha approximate to 89.2 degrees, ss approximate to 94.6 degrees, gamma 105.6 degrees; reflections: 414, overlapping, 232, and nonoverlapping, 182; resolution, 5.16 angstrom axial and 11.1 angstrom equatorial). This structure shows that the molecular packing topology of the collagen molecule is such that packing neighbors are arranged to form a supertwisted (discontinuous) right-handed microfibril that interdigitates with neighboring microfibrils. This interdigitation establishes the crystallographic superlattice, which is formed of quasihexagonally packed collagen molecules. In addition, the molecular packing structure of collagen shown here provides information concerning the potential modes of action of two prominent molecules involved in human health and disease: decorin and the Matrix Metallo-Proteinase (MMP) collagenase.