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使用“构建和检索”方法进行高分辨率结构蛋白质组学研究线粒体。

High-Resolution Structural Proteomics of Mitochondria Using the 'Build and Retrieve' Methodology.

机构信息

Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.

出版信息

Mol Cell Proteomics. 2023 Dec;22(12):100666. doi: 10.1016/j.mcpro.2023.100666. Epub 2023 Oct 14.

DOI:10.1016/j.mcpro.2023.100666
PMID:37839702
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10709515/
Abstract

The application of integrated systems biology to the field of structural biology is a promising new direction, although it is still in the infant stages of development. Here we report the use of single particle cryo-EM to identify multiple proteins from three enriched heterogeneous fractions prepared from human liver mitochondrial lysate. We simultaneously identify and solve high-resolution structures of nine essential mitochondrial enzymes with key metabolic functions, including fatty acid catabolism, reactive oxidative species clearance, and amino acid metabolism. Our methodology also identified multiple distinct members of the acyl-CoA dehydrogenase family. This work highlights the potential of cryo-EM to explore tissue proteomics at the atomic level.

摘要

将集成系统生物学应用于结构生物学领域是一个很有前途的新方向，尽管它仍处于发展的初期阶段。在这里，我们报告了使用单颗粒冷冻电镜从人肝线粒体裂解物制备的三种富集的异质级分中鉴定多种蛋白质。我们同时鉴定并解析了具有关键代谢功能的九种重要线粒体酶的高分辨率结构，包括脂肪酸分解代谢、活性氧清除和氨基酸代谢。我们的方法还鉴定了酰基辅酶 A 脱氢酶家族的多个不同成员。这项工作突出了冷冻电镜在原子水平上探索组织蛋白质组学的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/0107c4e95160/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/8a2e05c45417/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/d4b081c96937/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/76ffc01519a3/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/d51fdbc4e195/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/42e3a94eb684/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/000065bd3ea9/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/89fabd0c2cb3/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/16e3515320b5/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/abe6aebdaeb7/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/0107c4e95160/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/8a2e05c45417/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/d4b081c96937/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/76ffc01519a3/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/d51fdbc4e195/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/42e3a94eb684/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/000065bd3ea9/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/89fabd0c2cb3/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/16e3515320b5/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/abe6aebdaeb7/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2251/10709515/0107c4e95160/gr9.jpg

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