RT Journal Article
SR Electronic
T1 Global analysis of methionine oxidation provides a census of folding stabilities for the human proteome
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 467290
DO 10.1101/467290
A1 Ethan J. Walker
A1 John Q. Bettinger
A1 Kevin A. Welle
A1 Jennifer R. Hryhorenko
A1 Sina Ghaemmaghami
YR 2018
UL http://biorxiv.org/content/early/2018/11/09/467290.abstract
AB The stability of proteins influences their tendency to aggregate, undergo degradation or become modified in cells. Despite their significance to understanding protein folding and function, quantitative analyses of thermodynamic stabilities have been mostly limited to soluble proteins in purified systems. We have used a highly multiplexed proteomics approach, based on analyses of methionine oxidation rates, to quantify stabilities of ~10,000 unique regions within ~3,000 proteins in human cell extracts. The data identify lysosomal and extracellular proteins as the most stable ontological subsets of the proteome. We show that the stability of proteins impacts their tendency to become oxidized and is globally altered by the osmolyte trimethylamine-N-oxide (TMAO). We also show that most proteins designated as intrinsically disordered retain their unfolded structure in the complex environment of the cell. Together, the data provide a census of the stability of the human proteome and validate a methodology for global quantitation of folding thermodynamics.