Hydroxyproline Ring Pucker Causes Frustration of Helix Parameters in the Collagen Triple Helix.
Hydroxyproline Ring Pucker Causes Frustration of Helix Parameters in the Collagen Triple Helix.
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DOI：
10.1038/srep12556
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发表时间：
2015-07-29
影响因子：
4.6
通讯作者：
Duer MJ
中科院分区：
文献类型：
--
作者：
Chow WY;Bihan D;Forman CJ;Slatter DA;Reid DG;Wales DJ;Farndale RW;Duer MJ
胶原蛋白是哺乳动物中最丰富的蛋白质，由其三螺旋结构和独特的Gly-Xaa-Yaa重复序列定义，其中Xaa通常是脯氨酸，Yaa是羟脯氨酸（Hyp/O）。已知Yaa位置的羟脯氨酸稳定三螺旋，并且由于一系列因素如水合性质的变化，体内缺乏脯氨酸羟基化导致胶原细胞外基质组装功能障碍。此外，我们注意到，在模型肽中，当Yaa是未修饰的脯氨酸时，Xaa脯氨酸具有采用内环构象的强烈倾向，而当Yaa是羟脯氨酸时，Xaa脯氨酸采用一系列的内和外构象。在这里，我们使用固态NMR光谱和合成三螺旋胶原蛋白肽的势能景观建模的组合来理解这种效果。我们表明，羟基化的Yaa脯氨酸导致Xaa脯氨酸环构象成为亚稳态，这反过来又赋予灵活性的三螺旋。
Collagens, the most abundant proteins in mammals, are defined by their triple-helical structures and distinctive Gly-Xaa-Yaa repeating sequence, where Xaa is often proline and Yaa, hydroxyproline (Hyp/O). It is known that hydroxyproline in the Yaa position stabilises the triple helix, and that lack of proline hydroxylation in vivo leads to dysfunctional collagen extracellular matrix assembly, due to a range of factors such as a change in hydration properties. In addition, we note that in model peptides, when Yaa is unmodified proline, the Xaa proline has a strong propensity to adopt an endo ring conformation, whilst when Yaa is hydroxyproline, the Xaa proline adopts a range of endo and exo conformations. Here we use a combination of solid-state NMR spectroscopy and potential energy landscape modelling of synthetic triple-helical collagen peptides to understand this effect. We show that hydroxylation of the Yaa proline causes the Xaa proline ring conformation to become metastable, which in turn confers flexibility on the triple helix.