Keenan E Keith, Zachman Derek K, Hirschey Matthew D
Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27701, USA; Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27701, USA.
Mol Cell. 2021 May 6;81(9):1868-1878. doi: 10.1016/j.molcel.2021.03.015. Epub 2021 Apr 1.
Protein modifications modulate nearly every aspect of cell biology in organisms, ranging from Archaea to Eukaryotes. The earliest evidence of covalent protein modifications was found in the early 20th century by studying the amino acid composition of proteins by chemical hydrolysis. These discoveries challenged what defined a canonical amino acid. The advent and rapid adoption of mass-spectrometry-based proteomics in the latter part of the 20th century enabled a veritable explosion in the number of known protein modifications, with more than 500 discrete modifications counted today. Now, new computational tools in data science, machine learning, and artificial intelligence are poised to allow researchers to make significant progress in discovering new protein modifications and determining their function. In this review, we take an opportunity to revisit the historical discovery of key post-translational modifications, quantify the current landscape of covalent protein adducts, and assess the role that new computational tools will play in the future of this field.
蛋白质修饰几乎调节了从古细菌到真核生物等生物体细胞生物学的各个方面。共价蛋白质修饰的最早证据是在20世纪初通过化学水解研究蛋白质的氨基酸组成时发现的。这些发现挑战了对标准氨基酸的定义。20世纪后期基于质谱的蛋白质组学的出现和迅速采用，使得已知蛋白质修饰的数量真正激增，如今已统计出500多种不同的修饰。现在，数据科学、机器学习和人工智能领域的新计算工具有望使研究人员在发现新的蛋白质修饰及其功能确定方面取得重大进展。在本综述中，我们借此机会回顾关键翻译后修饰的历史发现，量化共价蛋白质加合物的当前情况，并评估新计算工具在该领域未来将发挥的作用。
