瑞士苏黎世联邦理工学院Helma Wennemers研究团队实验与理论研究脂质化对胶原三螺旋折叠及稳定性的影响。 相关研究成果于2021年4月8日发表在国际顶尖学术期刊《美国化学会杂志》。

三螺旋胶原是自然界中含量最丰富的蛋白质，其折叠依赖于成核和沿链传播。疏水部分对许多蛋白质的折叠和稳定性至关重要。相反，大自然利用胶原三聚结构域和顺反脯氨酰异构酶来促进和加速三螺旋的形成。然而，悬垂的疏水部分赋予了三螺旋胶原超稳定性，并加速了顺反异构化，使胶原三螺旋在热诱导下以相同的速度展开和折叠。

该文中，研究人员系统地探讨了侧链脂肪酸对胶原三螺旋折叠和稳定性的影响。一系列含有不同长度的饱和和不饱和脂肪酸的胶原模拟肽（CMPs）的热变性和动力学研究表明，更长和更灵活的脂肪酸附属物增加了胶原三螺旋的稳定性和折叠速率。分子动力学模拟结合实验数据表明，疏水性附属物通过与胶原三螺旋槽的相互作用稳定了三螺旋，并通过形成熔融的球状中间物加速了折叠和展开过程。

附：英文原文

Title: Influence of Lipidation on the Folding and Stability of Collagen Triple Helices—An Experimental and Theoretical Study

Author: Jasmine Egli, Carmen Esposito, Mike Müri, Sereina Riniker, Helma Wennemers

Issue&Volume: April 8, 2021

Abstract: The folding of triple-helical collagen, the most abundant protein in nature, relies on the nucleation and propagation along the strands. Hydrophobic moieties are crucial for the folding and stability of numerous proteins. Instead, nature uses for collagen a trimerization domain and cis-trans prolyl isomerases to facilitate and accelerate triple helix formation. Yet, pendant hydrophobic moieties endow triple-helical collagen with hyperstability and accelerate the cis-trans isomerization to an extent that thermally induced unfolding and folding of collagen triple helices take place at the same speed. Here, we systematically explored the effect of pendant fatty acids on the folding and stability of collagen triple helices. Thermal denaturation and kinetic studies with a series of collagen mimetic peptides (CMPs) bearing saturated and unsaturated fatty acids with different lengths revealed that longer and more flexible fatty acid appendages increase the stability and the folding rate of collagen triple helices. Molecular dynamics simulations combined with experimental data indicate that the hydrophobic appendages stabilize the triple helix by interaction with the grooves of the collagen triple helix and accelerate the folding and unfolding process by creating a molten globule-like intermediate.

DOI: 10.1021/jacs.1c01512

Source: https://pubs.acs.org/doi/10.1021/jacs.1c01512