Chain registry and load-dependent conformational dynamics of collagen.
Chain registry and load-dependent conformational dynamics of collagen.
复制标题
胶原蛋白的链登记和负载依赖性构象动力学。
DOI：
10.1021/bm500641f
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发表时间：
2014
影响因子：
6.2
通讯作者：
Hwang,Wonmuk
中科院分区：
文献类型：
--
作者：
Teng,Xiaojing;Hwang,Wonmuk
纤维状胶原蛋白的降解对于组织维护至关重要。然而，理解胶原蛋白catalysts一直是具有挑战性的，部分原因是缺乏其负载依赖性构象动力学的原子图像，因为机械负载和局部展开的胶原蛋白影响其裂解基质金属蛋白酶（MMP）。我们使用分子动力学模拟来寻找胶原蛋白三螺旋中最容易切割的α链排列，并根据分子内的链登记找到调节MMP切割结构域稳定性的氨基酸。天然样状态是机械不均匀的，其中切割位点沿着分子与刚性区域和局部未折叠和柔性区域交界。相比之下，由稳定的甘氨酸-脯氨酸-羟脯氨酸基序组成的三螺旋是均匀柔性的，并且通过短寿命、低占有率的氢键动态稳定。这些结果为胶原的力学、构象和稳定性提供了原子基础。
Degradation of fibrillar collagen is critical for tissue maintenance. Yet, understanding collagen catabolism has been challenging partly due to a lack of atomistic picture for its load-dependent conformational dynamics, as both mechanical load and local unfolding of collagen affect its cleavage by matrix metalloproteinase (MMP). We use molecular dynamics simulation to find the most cleavage-prone arrangement of α chains in a collagen triple helix and find amino acids that modulate stability of the MMP cleavage domain depending on the chain registry within the molecule. The native-like state is mechanically inhomogeneous, where the cleavage site interfaces a stiff region and a locally unfolded and flexible region along the molecule. In contrast, a triple helix made of the stable glycine-proline-hydroxyproline motif is uniformly flexible and is dynamically stabilized by short-lived, low-occupancy hydrogen bonds. These results provide an atomistic basis for the mechanics, conformation, and stability of collagen that affect catabolism.