科學家揭示蛋白質高解析度功能改變
作者：
小柯機器人發布時間：2020/12/25 14:57:41
瑞士蘇黎世聯邦理工學院生物系Paola Picotti課題組取得最新進展。他們利用動態3D蛋白質組在高解析度下原位揭示蛋白質功能改變。該項研究成果發表在2020年12月23日出版的《細胞》雜誌上。
他們在這裡證明，基於有限的蛋白水解質譜（LiP-MS）的全球蛋白質結構輸出可同時和原位檢測正在經歷營養適應的細菌和響應急性應激的酵母中許多此類功能改變。結構輸出，可視為結構條形碼，捕獲的酶活性變化、磷酸化、蛋白質聚集和複合物形成，具有單個調節功能位點（例如結合位點和活性位點）的解析度。與包括其他組學數據在內的現有認知的比較表明，LiP-MS可在經過充分研究的途徑中檢測到許多已知的功能改變。它提出了獨特的代謝物-蛋白質相互作用，並使得能夠鑑定基於果糖-1,6-二磷酸的葡萄糖在大腸桿菌中的調節機制。結構輸出極大地增加了經典蛋白質組學的覆蓋範圍，產生了機械學假說，並為原位結構系統生物學鋪平了道路。
據介紹，生物過程受到分子間相互作用和不影響蛋白質水平的化學修飾的調節，從而避免了經典蛋白質組學篩選中的檢測。
附：英文原文
Title: Dynamic 3D proteomes reveal protein functional alterations at high resolution in situ
Author: Valentina Cappelletti, Thomas Hauser, Ilaria Piazza, Monika Pepelnjak, Liliana Malinovska, Tobias Fuhrer, Yaozong Li, Christian Drig, Paul Boersema, Ludovic Gillet, Jan Grossbach, Aurelien Dugourd, Julio Saez-Rodriguez, Andreas Beyer, Nicola Zamboni, Amedeo Caflisch, Natalie de Souza, Paola Picotti
Issue&Volume: 2020-12-23
Abstract: Biological processes are regulated by intermolecular interactions and chemical modifications that do not affect protein levels, thus escaping detection in classical proteomic screens. We demonstrate here that a global protein structural readout based on limited proteolysis-mass spectrometry (LiP-MS) detects many such functional alterations, simultaneously and in situ, in bacteria undergoing nutrient adaptation and in yeast responding to acute stress. The structural readout, visualized as structural barcodes, captured enzyme activity changes, phosphorylation, protein aggregation, and complex formation, with the resolution of individual regulated functional sites such as binding and active sites. Comparison with prior knowledge, including other 『omics data, showed that LiP-MS detects many known functional alterations within well-studied pathways. It suggested distinct metabolite-protein interactions and enabled identification of a fructose-1,6-bisphosphate-based regulatory mechanism of glucose uptake in E. coli. The structural readout dramatically increases classical proteomics coverage, generates mechanistic hypotheses, and paves the way for in situ structural systems biology.
DOI: 10.1016/j.cell.2020.12.021
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31691-3
Cell：《細胞》，創刊於1974年。隸屬於細胞出版社，最新IF：36.216