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

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

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

Fingerprint

Mutant Proteins
mutants
Chemical activation
Signal transduction
Mutagenesis
Proteins
proteins
deuterium
Deuterium
X ray crystallography
X Ray Crystallography
site-directed mutagenesis
amides
Site-Directed Mutagenesis
Amides
X-ray diffraction
Glycine
hydrogen
Mass spectrometry
signal transduction

ASJC Scopus subject areas

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

Cite this

Structural Analyses of a Constitutively Active Mutant of Exchange Protein Directly Activated by cAMP. / White, Mark; Li, Sheng; Tsalkova, Tamara; Mei, Fang C.; Liu, Tong; Woods, Virgil L.; Cheng, Xiaodong.

In: PLoS One, Vol. 7, No. 11, e49932, 26.11.2012.

Research output: Contribution to journalArticle

White, Mark ; Li, Sheng ; Tsalkova, Tamara ; Mei, Fang C. ; Liu, Tong ; Woods, Virgil L. ; Cheng, Xiaodong. / Structural Analyses of a Constitutively Active Mutant of Exchange Protein Directly Activated by cAMP. In: PLoS One. 2012 ; Vol. 7, No. 11.
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