Structural highlights
Function
[RPGF4_MOUSE] Guanine nucleotide exchange factor (GEF) for RAP1A, RAP1B and RAP2A small GTPases that is activated by binding cAMP. Seems not to activate RAB3A. Involved in cAMP-dependent, PKA-independent exocytosis through interaction with RIMS2.[1]
Publication Abstract from PubMed
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.
Structural analyses of a constitutively active mutant of exchange protein directly activated by cAMP.,White MA, Li S, Tsalkova T, Mei FC, Liu T, Woods VL Jr, Cheng X PLoS One. 2012;7(11):e49932. doi: 10.1371/journal.pone.0049932. Epub 2012 Nov 26. PMID:23189173[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ozaki N, Shibasaki T, Kashima Y, Miki T, Takahashi K, Ueno H, Sunaga Y, Yano H, Matsuura Y, Iwanaga T, Takai Y, Seino S. cAMP-GEFII is a direct target of cAMP in regulated exocytosis. Nat Cell Biol. 2000 Nov;2(11):805-11. PMID:11056535 doi:http://dx.doi.org/10.1038/35041046
- ↑ White MA, Li S, Tsalkova T, Mei FC, Liu T, Woods VL Jr, Cheng X. Structural analyses of a constitutively active mutant of exchange protein directly activated by cAMP. PLoS One. 2012;7(11):e49932. doi: 10.1371/journal.pone.0049932. Epub 2012 Nov 26. PMID:23189173 doi:http://dx.doi.org/10.1371/journal.pone.0049932
