Docking Interactions Induce Exposure of Activation Loop in the MAP Kinase ERK2

Tianjun Zhou, Liguang Sun, John Humphreys, Elizabeth J. Goldsmith

Research output: Contribution to journalArticle

120 Scopus citations

Abstract

MAP kinases bind activating kinases, phosphatases, and substrates through docking interactions. Here, we report a 1.9 Å crystallographic analysis of inactive ERK2 bound to a "D motif" docking peptide (pepHePTP) derived from hematopoietic tyrosine phosphatase, a negative regulator of ERK2. In this complex, the complete D motif interaction defined by mutagenic analysis is observed, including extensive electrostatic interactions with the "CD" site of the kinase. Large conformational changes occur in the activation loop where the dual phosphorylation sites, which are buried in the inactive form of ERK2, become exposed to solvent in the complex. Similar conformational changes occur in a complex between ERK2 and a MEK2 (MAP/ERK kinase-2)-derived D motif peptide (pepMEK2). D motif peptides are known to bind homologous loci in the MAP kinases p38α and JNK1, also inducing conformational changes in these enzymes. However, the binding interactions and conformational changes are unique to each, thus contributing to specificity among MAP kinases.

Original languageEnglish (US)
Pages (from-to)1011-1019
Number of pages9
JournalStructure
Volume14
Issue number6
DOIs
StatePublished - Jun 1 2006

Keywords

  • SIGNALING

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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