Meltome atlas-thermal proteome stability across the tree of life

Mass Spectrometry-Based Analysis of Proteome-Wide Protein Stability

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.

 

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Jarzab A, Kurzawa N, Hopf T*, Moerch M, Zecha J, Leijten N, Bian Y, Musiol E, Maschberger M, Stoehr G*, Becher I, Daly C, Samaras P, Meraner J, Spanier B, Angelov A, Werner T, Bantscheff M, Wilhelm M^†, Klingenspor M, Lemeer S, Liebl W, Hahne H*, Savitski MM & Kuster B^†. Meltome atlas-thermal proteome stability across the tree of life. Nature Methods 17, 495-403 (2020).

*Momentum Employee (or former OmicScouts employee)
^†Momentum Scientific Advisory Board Member

 

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