Alpha-突触核蛋白与完整线粒体相互作用的NMR研究
收稿日期: 2020-07-07
网络出版日期: 2020-09-01
基金资助
国家自然科学基金资助项目(21505152);国家自然科学基金资助项目(21673284);国家自然科学基金资助项目(21203243);国家自然科学基金资助项目(21874149);国家自然科学基金资助项目(21925406)
Interactions Between α-synuclein and Intact Mitochondria Studied by NMR
Received date: 2020-07-07
Online published: 2020-09-01
天然无结构蛋白alpha-突触核蛋白（α-synuclein）能影响线粒体的形态、动力学及损害线粒体正常功能，被认为是帕金森症的致病机制之一.α-synuclein与线粒体模拟膜及分离提取的完整线粒体的相互作用研究是理解该蛋白如何影响线粒体的有效途径.文献报道α-synuclein能与磷脂模拟的线粒体内膜相互作用却不与模拟的外膜相互作用，且N端在与线粒体的结合中扮演重要角色，但具体的作用位点仍不十分清楚.本文利用核磁共振（NMR）方法研究了α-synuclein与大鼠肝脏中分离的完整线粒体的相互作用，发现α-synuclein能与线粒体外膜相互作用，且作用区域位于α-synuclein N端的前60个氨基酸残基.这一结果与文献报道并不相同，可能是因为α-synuclein与线粒体外膜的作用不仅依赖于膜组分，可能也和膜的曲率或膜上其他组分等相关，而这些是模拟膜所不易体现的.同时，我们的研究也证实NMR是研究蛋白质与分离完整线粒体相互作用的有效方法.
关键词： 核磁共振(NMR); alpha-突触核蛋白; 完整线粒体; 相互作用
余锦波 , 张偲 , 张则婷 , 徐国华 , 李从刚 . Alpha-突触核蛋白与完整线粒体相互作用的NMR研究[J]. 波谱学杂志, 2021 , 38(2) : 164 -172 . DOI: 10.11938/cjmr20202841
The intrinsically disordered alpha-synuclein (α-synuclein) directly affects mitochondrial dynamics, morphology and function, and is closely related to Parkinson's disease. Studying the interactions between α-synuclein and mimic mitochondrial membranes/intact mitochondria is an effective way to understand how α-synuclein affects mitochondria. It has been reported that α-synuclein interacts with the mimic inner membrane of mitochondria (IMM), but not with the outer membrane of mitochondria (OMM), and the N-terminal plays an important role in binding with the mitochondria. However, little is known about the positions of interaction. Here, the interactions between α-synuclein and intact mitochondria isolated from rat liver were investigated by nuclear magnetic resonance (NMR). It was found that, different from the previous report, α-synuclein interacted with the OMM and the first 60 residues of N-terminus were crucial for the binding. It was postulated that the interaction between α-synuclein and OMM might depend not only on the lipid composition of the membrane, but also on other factors which were not reflected in the mimic membrane, such as the curvature of membrane and/or other components of the OMM. Our study also indicated that NMR is an effective method for studying the interaction of proteins with intact mitochondria.
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