Journal article

Hidden information on protein function in censuses of proteome foldedness

Dezerae Cox, Ching-Seng Ang, Nadinath Nillegoda, Gavin Reid, Danny Hatters

Cold Spring Harbor Laboratory | Published : 2021

Abstract

Methods: that assay protein foldedness with proteomics have generated censuses of protein folding stabilities in biological milieu. Surprisingly, different censuses poorly correlate with each other. Here, we show that methods targeting foldedness through monitoring amino acid sidechain reactivity also detect changes in conformation and ligand binding. About one quarter of cysteine or methionine sidechains in proteins in mammalian cell lysate increase in reactivity upon chemical denaturant titration consistent with two-state unfolding. Paradoxically, up to one third decreased reactivity, which were enriched in proteins with functions relating to unfolded protein stress. One protein, chaperon..

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