Temperature influences the physiology of all living matter. Some organisms live in cold environments, most eukaryotes die when their inner temperature increases above 42 °C, but some species can survive even in hot springs. As most processes in life are regulated by proteins, we systematically recorded the thermal stability of proteins across 13 different species to better understand the diversity of protein structure and function.
Together with colleagues from the EMBL, Cellzome and OmicScouts, 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 exemplify cases where 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 Meltome and ProteomicsDB.