Disordered Filaments Mediate the Fibrillogenesis of Type I Collagen in Solution.
Disordered Filaments Mediate the Fibrillogenesis of Type I Collagen in Solution.
复制标题
无序的细丝介导溶液中 I 型胶原蛋白的纤维形成。
DOI：
10.1021/acs.biomac.0c00667
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发表时间：
2020
影响因子：
6.2
通讯作者：
McCluskey AR
中科院分区：
文献类型：
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作者：
McCluskey AR
I型胶原蛋白是哺乳动物中的主要结构蛋白之一，为角膜、肌腱、骨、皮肤和牙本质等组织提供机械稳定性、强度和韧性。胶原原纤维由排列成四分之一交错阵列的胶原分子组成，其产生沿原纤维轴沿着67 nm的周期性，具有30 nm的重叠区和37 nm的间隙区。这种高度组织化的原纤维的形成是一个自组装过程，其中静电和疏水相互作用在确定具有67 nm周期性的分子的交错中起关键作用。虽然胶原蛋白自组装已被广泛研究，但对机制知之甚少，特别是最初形成的核的性质，聚集过程的不同阶段，以及分子如何组织成原纤维。通过结合时间分辨低温透射电子显微镜与分子动力学模拟，我们表明，胶原蛋白组装是一个多步骤的过程中，分子首先形成细丝，自组织成纤维与无序结构。D-带周期性的出现是逐渐的，并且开始于分子的N-末端处的相邻细丝的对齐，首先导致具有67 nm的周期性的带，然后形成间隙和重叠区域。
Collagen type I is one of the major structural proteins in mammals, providing tissues such as cornea, tendon, bone, skin, and dentin with mechanical stability, strength, and toughness. Collagen fibrils are composed of collagen molecules arranged in a quarter-stagger array that gives rise to a periodicity of 67 nm along the fibril axis, with a 30 nm overlap zone and a 37 nm gap zone. The formation of such highly organized fibrils is a self-assembly process where electrostatic and hydrophobic interactions play a critical role in determining the staggering of the molecules with 67 nm periodicity. While collagen self-assembly has been extensively studied, not much is known about the mechanism, and in particular, the nature of the nuclei that initially form, the different stages of the aggregation process, and how the organization of the molecules into fibrils arises. By combining time-resolved cryo-transmission electron microscopy with molecular dynamics simulations, we show that collagen assembly is a multistep process in which the molecules first form filaments which self-organize into fibrils with a disordered structure. The appearance of the D-band periodicity is gradual and starts with the alignment of adjacent filaments at the N-terminal end of the molecules, first leading to bands with a periodicity of 67 nm and then to the formation of gap and overlap regions.