Phosphorylation releases constraints to domain motion in ERK2.

Yao Xiao, Thomas Lee, Michael Latham, Lisa Rose Warner, Akiko Tanimoto, Arthur Pardi, Natalie G Ahn

Research output: Contribution to journalArticle

Abstract

Protein motions control enzyme catalysis through mechanisms that are incompletely understood. Here NMR (13)C relaxation dispersion experiments were used to monitor changes in side-chain motions that occur in response to activation by phosphorylation of the MAP kinase ERK2. NMR data for the methyl side chains on Ile, Leu, and Val residues showed changes in conformational exchange dynamics in the microsecond-to-millisecond time regime between the different activity states of ERK2. In inactive, unphosphorylated ERK2, localized conformational exchange was observed among methyl side chains, with little evidence for coupling between residues. Upon dual phosphorylation by MAP kinase kinase 1, the dynamics of assigned methyls in ERK2 were altered throughout the conserved kinase core, including many residues in the catalytic pocket. The majority of residues in active ERK2 fit to a single conformational exchange process, with kex ≈ 300 s(-1) (kAB ≈ 240 s(-1)/kBA ≈ 60 s(-1)) and pA/pB ≈ 20%/80%,
Original languageEnglish
Pages (from-to)2506–11
JournalProceedings of the National Academy of Sciences of the United States of America
DOIs
StatePublished - Feb 2014

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