학술논문
Structural Analyses of a Constitutively Active Mutant of Exchange Protein Directly Activated by cAMP.
Document Type
Article
Author
Source
Subject
*TRANSCRIPTION factors
*INTERLEUKIN-8
*CELL differentiation
*MICROGLIA
*MORPHOLOGY
*BIOMARKERS
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*
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Language
ISSN
1932-6203
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. [ABSTRACT FROM AUTHOR]