Structural analyses of a constitutively active mutant of exchange protein directly activated by cAMP.

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 ex...

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Autores principales:	Mark A White, Sheng Li, Tamara Tsalkova, Fang C Mei, Tong Liu, Virgil L Woods, Xiaodong Cheng
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e4407aa16482427d8aea4f83e9dc9941
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spelling	oai:doaj.org-article:e4407aa16482427d8aea4f83e9dc99412021-11-18T08:07:36ZStructural analyses of a constitutively active mutant of exchange protein directly activated by cAMP.1932-620310.1371/journal.pone.0049932https://doaj.org/article/e4407aa16482427d8aea4f83e9dc99412012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23189173/?tool=EBIhttps://doaj.org/toc/1932-6203Exchange 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.Mark A WhiteSheng LiTamara TsalkovaFang C MeiTong LiuVirgil L WoodsXiaodong ChengPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e49932 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mark A White Sheng Li Tamara Tsalkova Fang C Mei Tong Liu Virgil L Woods Xiaodong Cheng Structural analyses of a constitutively active mutant of exchange protein directly activated by cAMP.
description	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.
format	article
author	Mark A White Sheng Li Tamara Tsalkova Fang C Mei Tong Liu Virgil L Woods Xiaodong Cheng
author_facet	Mark A White Sheng Li Tamara Tsalkova Fang C Mei Tong Liu Virgil L Woods Xiaodong Cheng
author_sort	Mark A White
title	Structural analyses of a constitutively active mutant of exchange protein directly activated by cAMP.
title_short	Structural analyses of a constitutively active mutant of exchange protein directly activated by cAMP.
title_full	Structural analyses of a constitutively active mutant of exchange protein directly activated by cAMP.
title_fullStr	Structural analyses of a constitutively active mutant of exchange protein directly activated by cAMP.
title_full_unstemmed	Structural analyses of a constitutively active mutant of exchange protein directly activated by cAMP.
title_sort	structural analyses of a constitutively active mutant of exchange protein directly activated by camp.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/e4407aa16482427d8aea4f83e9dc9941
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_version_	1718422201596641280

Structural analyses of a constitutively active mutant of exchange protein directly activated by cAMP.

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