Wiley Open Access, FASEB Journal, S1(32), 2018
DOI: 10.1096/fasebj.2018.32.1_supplement.533.100
National Academy of Sciences, Proceedings of the National Academy of Sciences, 51(114), p. 13453-13458, 2017
Full text: Download
Significance Phosphorylation is a ubiquitous modification that has been implicated in signaling and other functions, but the atomic-level mechanisms are not completely understood. We identify a salt-bridge competition or “theft” mechanism wherein a phosphoserine, but not a phosphomimetic, breaks a pre-existing salt bridge, initiating a partial unfolding event and promoting new protein interactions. Structural elements underlying the theft occurred early in evolution and are found in 10% of homo-oligomers and 30% of hetero-oligomers. These findings identify a facile and evolutionarily accessible mechanism for reorganizing salt bridges and other electrostatic networks with only a single mutation to trigger a functional switch.