原位
生物
蛋白质组
蛋白质组学
蛋白质水解
计算生物学
生物化学
细胞生物学
质谱法
生物物理学
酶
基因
化学
色谱法
有机化学
作者
Valentina Cappelletti,Thomas Häuser,Ilaria Piazza,Monika Pepelnjak,Liliana Malinovska,Tobias Fuhrer,Yaozong Li,Christian Dörig,Paul J. Boersema,Ludovic Gillet,Jan Großbach,Aurélien Dugourd,Julio Sáez-Rodríguez,Andreas Beyer,Nicola Zamboni,Amedeo Caflisch,Natalie de Souza,Paola Picotti
出处
期刊:Cell
[Elsevier]
日期:2020-12-23
卷期号:184 (2): 545-559.e22
被引量:110
标识
DOI:10.1016/j.cell.2020.12.021
摘要
SUMMARY
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.
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