美国莱斯大学Hartgerink Jeffrey D.团队报了具有高特异性组装的异三聚体胶原螺旋导致快速折叠。相关研究成果发表在2024年7月15日出版的《自然—化学》。

最丰富的天然胶原蛋白形成异三聚体三螺旋。研究人员发现胶原异三聚体的合成模拟物折叠缓慢，甚至与已经很慢的同源三聚体螺旋相比更慢。这些长时间的折叠率尚不清楚。

该文中，研究人员比较了通过计算辅助方法设计的，三种异三聚体胶原模拟物的稳定性、特异性和折叠率。一个ABC型异三聚体的晶体结构验证了一个控制良好的组成和记录，并阐明了组件中成对阳离子π和轴向和横向盐桥的几何形状。这种胶原蛋白异三聚体的折叠速度（数小时比数天）比设计良好的同类系统快得多。

圆二色性和核磁共振数据表明，这种折叠受到非生产性、竞争性异三聚体物种的阻碍，这些物种在折叠成热力学上有利的组装体之前必须先展开。引入预先形成的竞争性三螺旋组件抑制了异三聚体胶原的折叠速率，这表明缓慢的异三聚体折叠动力学主要是由，竞争性三螺纹引起的能量景貌的抑制所主导的。

附：英文原文

Title: Heterotrimeric collagen helix with high specificity of assembly results in a rapid rate of folding

Author: Cole, Carson C., Walker, Douglas R., Hulgan, Sarah A. H., Pogostin, Brett H., Swain, Joseph W. R., Miller, Mitchell D., Xu, Weijun, Duella, Ryan, Misiura, Mikita, Wang, Xu, Kolomeisky, Anatoly B., Philips, George N., Hartgerink, Jeffrey D.

Issue&Volume: 2024-07-15

Abstract: The most abundant natural collagens form heterotrimeric triple helices. Synthetic mimics of collagen heterotrimers have been found to fold slowly, even compared to the already slow rates of homotrimeric helices. These prolonged folding rates are not understood. Here we compare the stabilities, specificities and folding rates of three heterotrimeric collagen mimics designed through a computationally assisted approach. The crystal structure of one ABC-type heterotrimer verified a well-controlled composition and register and elucidated the geometry of pairwise cation–π and axial and lateral salt bridges in the assembly. This collagen heterotrimer folds much faster (hours versus days) than comparable, well-designed systems. Circular dichroism and NMR data suggest the folding is frustrated by unproductive, competing heterotrimer species and these species must unwind before refolding into the thermodynamically favoured assembly. The heterotrimeric collagen folding rate is inhibited by the introduction of preformed competing triple-helical assemblies, which suggests that slow heterotrimer folding kinetics are dominated by the frustration of the energy landscape caused by competing triple helices.

DOI: 10.1038/s41557-024-01573-2

Source: https://www.nature.com/articles/s41557-024-01573-2