1o7f
From Proteopedia
(New page: 200px<br /><applet load="1o7f" size="450" color="white" frame="true" align="right" spinBox="true" caption="1o7f, resolution 2.5Å" /> '''CRYSTAL STRUCTURE OF ...) |
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| - | [[Image:1o7f.jpg|left|200px]]<br /><applet load="1o7f" size=" | + | [[Image:1o7f.jpg|left|200px]]<br /><applet load="1o7f" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1o7f, resolution 2.5Å" /> | caption="1o7f, resolution 2.5Å" /> | ||
'''CRYSTAL STRUCTURE OF THE REGULATORY DOMAIN OF EPAC2'''<br /> | '''CRYSTAL STRUCTURE OF THE REGULATORY DOMAIN OF EPAC2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Cyclic adenosine monophosphate (cAMP) is a universal second messenger | + | Cyclic adenosine monophosphate (cAMP) is a universal second messenger that, in eukaryotes, was believed to act only on cAMP-dependent protein kinase A (PKA) and cyclic nucleotide-regulated ion channels. Recently, guanine nucleotide exchange factors specific for the small GTP-binding proteins Rap1 and Rap2 (Epacs) were described, which are also activated directly by cAMP. Here, we have determined the three-dimensional structure of the regulatory domain of Epac2, which consists of two cyclic nucleotide monophosphate (cNMP)-binding domains and one DEP (Dishevelled, Egl, Pleckstrin) domain. This is the first structure of a cNMP-binding domain in the absence of ligand, and comparison with previous structures, sequence alignment and biochemical experiments allow us to delineate a mechanism for cyclic nucleotide-mediated conformational change and activation that is most likely conserved for all cNMP-regulated proteins. We identify a hinge region that couples cAMP binding to a conformational change of the C-terminal regions. Mutations in the hinge of Epac can uncouple cAMP binding from its exchange activity. |
==About this Structure== | ==About this Structure== | ||
| - | 1O7F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http:// | + | 1O7F is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1O7F OCA]. |
==Reference== | ==Reference== | ||
| - | Structure and regulation of the cAMP-binding domains of Epac2., Rehmann H, Prakash B, Wolf E, Rueppel A, | + | Structure and regulation of the cAMP-binding domains of Epac2., Rehmann H, Prakash B, Wolf E, Rueppel A, de Rooij J, Bos JL, Wittinghofer A, Nat Struct Biol. 2003 Jan;10(1):26-32. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12469113 12469113] |
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Bos, J | + | [[Category: Bos, J L.]] |
[[Category: Prakash, B.]] | [[Category: Prakash, B.]] | ||
[[Category: Rehmann, H.]] | [[Category: Rehmann, H.]] | ||
| - | [[Category: Rooij, J | + | [[Category: Rooij, J De.]] |
[[Category: Rueppel, A.]] | [[Category: Rueppel, A.]] | ||
[[Category: Wittinghofer, A.]] | [[Category: Wittinghofer, A.]] | ||
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[[Category: regulation]] | [[Category: regulation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:14:24 2008'' |
Revision as of 12:14, 21 February 2008
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CRYSTAL STRUCTURE OF THE REGULATORY DOMAIN OF EPAC2
Overview
Cyclic adenosine monophosphate (cAMP) is a universal second messenger that, in eukaryotes, was believed to act only on cAMP-dependent protein kinase A (PKA) and cyclic nucleotide-regulated ion channels. Recently, guanine nucleotide exchange factors specific for the small GTP-binding proteins Rap1 and Rap2 (Epacs) were described, which are also activated directly by cAMP. Here, we have determined the three-dimensional structure of the regulatory domain of Epac2, which consists of two cyclic nucleotide monophosphate (cNMP)-binding domains and one DEP (Dishevelled, Egl, Pleckstrin) domain. This is the first structure of a cNMP-binding domain in the absence of ligand, and comparison with previous structures, sequence alignment and biochemical experiments allow us to delineate a mechanism for cyclic nucleotide-mediated conformational change and activation that is most likely conserved for all cNMP-regulated proteins. We identify a hinge region that couples cAMP binding to a conformational change of the C-terminal regions. Mutations in the hinge of Epac can uncouple cAMP binding from its exchange activity.
About this Structure
1O7F is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
Reference
Structure and regulation of the cAMP-binding domains of Epac2., Rehmann H, Prakash B, Wolf E, Rueppel A, de Rooij J, Bos JL, Wittinghofer A, Nat Struct Biol. 2003 Jan;10(1):26-32. PMID:12469113
Page seeded by OCA on Thu Feb 21 14:14:24 2008
Categories: Mus musculus | Single protein | Bos, J L. | Prakash, B. | Rehmann, H. | Rooij, J De. | Rueppel, A. | Wittinghofer, A. | Wolf, E. | Camp | Camp-gef2 | Campb binding doamin | Epac2 | Exchange factor | Gef | Regulation
