Structural Analyses of a Constitutively Active Mutant of Exchange Protein Directly Activated by cAMP

Mark A. White, Sheng Li, Tamara Tsalkova, Fang C. Mei, Tong Liu, Virgil L. Woods, Xiaodong Cheng

Research output: Contribution to journalArticle

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Abstract

Exchange proteins directly activated by cAMP (EPACs) are important allosteric regulators of cAMP-mediated signal transduction pathways. To understand the molecular mechanism of EPAC activation, we have combined site-directed mutagenesis, X-ray crystallography, and peptide amide hydrogen/deuterium exchange mass spectrometry (DXMS) to probe the structural and conformational dynamics of EPAC2-F435G, a constitutively active EPAC2 mutant. Our study demonstrates that conformational dynamics plays a critical role in cAMP-induced EPAC activation. A glycine mutation at 435 position shifts the equilibrium of conformational dynamics towards the extended active conformation.

Original languageEnglish (US)
Article numbere49932
JournalPloS one
Volume7
Issue number11
DOIs
StatePublished - Nov 26 2012

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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