科學家繪製蛋白質組熱穩定性圖譜
作者:
小柯機器人發布時間:2020/4/19 23:00:44
德國慕尼黑工業大學Bernhard Kuster、歐洲分子生物學實驗室Mikhail M. Savitski、OmicScouts研究所Hannes Hahne等研究人員合作繪製了蛋白質組熱穩定性圖譜。該項研究成果於2020年4月13日在線發表於《自然—方法學》雜誌。
研究人員使用基於質譜的蛋白質組學方法,繪製了涵蓋從古細菌到人類13個物種中48,000種蛋白質的熱穩定性圖譜,涵蓋的變性溫度為30–90°C。蛋白質序列、組成和大小會影響原核生物的熱穩定性,而真核蛋白質則顯示出無序蛋白質結構程度與熱穩定性之間的非線性關係。
數據表明蛋白質複合物的進化保守性通過其蛋白質的相似熱穩定性反映出來,並且研究人員展示了基因組改變可影響熱穩定性的例子。他們發現呼吸鏈中的蛋白質在許多生物中非常穩定,在46°C時,人類線粒體的呼吸接近正常呼吸。
研究人員還注意到了可能影響蛋白質穩定性或藥物功效的細胞類型特異性作用。該基因組圖譜廣泛地定義了適用於生物學和藥物發現中熱分析的蛋白質組,可以在http://meltomeatlas.proteomics.wzw.tum.de:5003/和http://www.proteomicsdb.org上在線進行瀏覽。
附:英文原文
Title: Meltome atlas—thermal proteome stability across the tree of life
Author: Anna Jarzab, Nils Kurzawa, Thomas Hopf, Matthias Moerch, Jana Zecha, Niels Leijten, Yangyang Bian, Eva Musiol, Melanie Maschberger, Gabriele Stoehr, Isabelle Becher, Charlotte Daly, Patroklos Samaras, Julia Mergner, Britta Spanier, Angel Angelov, Thilo Werner, Marcus Bantscheff, Mathias Wilhelm, Martin Klingenspor, Simone Lemeer, Wolfgang Liebl, Hannes Hahne, Mikhail M. Savitski, Bernhard Kuster
Issue&Volume: 2020-04-13
Abstract: We have used a mass spectrometry-based proteomic approach to compile an atlas of the thermal stability of 48,000 proteins across 13 species ranging from archaea to humans and covering melting temperatures of 30–90°C. Protein sequence, composition and size affect thermal stability in prokaryotes and eukaryotic proteins show a nonlinear relationship between the degree of disordered protein structure and thermal stability. The data indicate that evolutionary conservation of protein complexes is reflected by similar thermal stability of their proteins, and we show examples in which genomic alterations can affect thermal stability. Proteins of the respiratory chain were found to be very stable in many organisms, and human mitochondria showed close to normal respiration at 46°C. We also noted cell-type-specific effects that can affect protein stability or the efficacy of drugs. This meltome atlas broadly defines the proteome amenable to thermal profiling in biology and drug discovery and can be explored online at http://meltomeatlas.proteomics.wzw.tum.de:5003/ and http://www.proteomicsdb.org.
DOI: 10.1038/s41592-020-0801-4
Source: https://www.nature.com/articles/s41592-020-0801-4