2g83
From Proteopedia
(New page: 200px<br /> <applet load="2g83" size="450" color="white" frame="true" align="right" spinBox="true" caption="2g83, resolution 2.8Å" /> '''Structure of activat...) |
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| - | [[Image:2g83.gif|left|200px]]<br /> | + | [[Image:2g83.gif|left|200px]]<br /><applet load="2g83" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="2g83, resolution 2.8Å" /> | caption="2g83, resolution 2.8Å" /> | ||
'''Structure of activated G-alpha-i1 bound to a nucleotide-state-selective peptide: Minimal determinants for recognizing the active form of a G protein alpha subunit'''<br /> | '''Structure of activated G-alpha-i1 bound to a nucleotide-state-selective peptide: Minimal determinants for recognizing the active form of a G protein alpha subunit'''<br /> | ||
==Overview== | ==Overview== | ||
| - | G-proteins cycle between an inactive GDP-bound state and an active | + | G-proteins cycle between an inactive GDP-bound state and an active GTP-bound state, serving as molecular switches that coordinate cellular signaling. We recently used phage display to identify a series of peptides that bind G alpha subunits in a nucleotide-dependent manner [Johnston, C. A., Willard, F. S., Jezyk, M. R., Fredericks, Z., Bodor, E. T., Jones, M. B., Blaesius, R., Watts, V. J., Harden, T. K., Sondek, J., Ramer, J. K., and Siderovski, D. P. (2005) Structure 13, 1069-1080]. Here we describe the structural features and functions of KB-1753, a peptide that binds selectively to GDP x AlF4(-)- and GTPgammaS-bound states of G alpha(i) subunits. KB-1753 blocks interaction of G alpha(transducin) with its effector, cGMP phosphodiesterase, and inhibits transducin-mediated activation of cGMP degradation. Additionally, KB-1753 interferes with RGS protein binding and resultant GAP activity. A fluorescent KB-1753 variant was found to act as a sensor for activated G alpha in vitro. The crystal structure of KB-1753 bound to G alpha(i1) x GDP x AlF4(-) reveals binding to a conserved hydrophobic groove between switch II and alpha3 helices and, along with supporting biochemical data and previous structural analyses, supports the notion that this is the site of effector interactions for G alpha(i) subunits. |
==About this Structure== | ==About this Structure== | ||
| - | 2G83 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ALF, MG and GDP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2G83 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ALF:'>ALF</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GDP:'>GDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G83 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Arshavsky, V | + | [[Category: Arshavsky, V Y.]] |
[[Category: Blaesius, R.]] | [[Category: Blaesius, R.]] | ||
| - | [[Category: Johnston, C | + | [[Category: Johnston, C A.]] |
[[Category: Kuhlman, B.]] | [[Category: Kuhlman, B.]] | ||
| - | [[Category: Ramer, J | + | [[Category: Ramer, J K.]] |
| - | [[Category: Siderovski, D | + | [[Category: Siderovski, D P.]] |
[[Category: ALF]] | [[Category: ALF]] | ||
[[Category: GDP]] | [[Category: GDP]] | ||
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[[Category: phage display peptide]] | [[Category: phage display peptide]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:29:05 2008'' |
Revision as of 15:29, 21 February 2008
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Structure of activated G-alpha-i1 bound to a nucleotide-state-selective peptide: Minimal determinants for recognizing the active form of a G protein alpha subunit
Overview
G-proteins cycle between an inactive GDP-bound state and an active GTP-bound state, serving as molecular switches that coordinate cellular signaling. We recently used phage display to identify a series of peptides that bind G alpha subunits in a nucleotide-dependent manner [Johnston, C. A., Willard, F. S., Jezyk, M. R., Fredericks, Z., Bodor, E. T., Jones, M. B., Blaesius, R., Watts, V. J., Harden, T. K., Sondek, J., Ramer, J. K., and Siderovski, D. P. (2005) Structure 13, 1069-1080]. Here we describe the structural features and functions of KB-1753, a peptide that binds selectively to GDP x AlF4(-)- and GTPgammaS-bound states of G alpha(i) subunits. KB-1753 blocks interaction of G alpha(transducin) with its effector, cGMP phosphodiesterase, and inhibits transducin-mediated activation of cGMP degradation. Additionally, KB-1753 interferes with RGS protein binding and resultant GAP activity. A fluorescent KB-1753 variant was found to act as a sensor for activated G alpha in vitro. The crystal structure of KB-1753 bound to G alpha(i1) x GDP x AlF4(-) reveals binding to a conserved hydrophobic groove between switch II and alpha3 helices and, along with supporting biochemical data and previous structural analyses, supports the notion that this is the site of effector interactions for G alpha(i) subunits.
About this Structure
2G83 is a Single protein structure of sequence from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
Reference
Minimal determinants for binding activated G alpha from the structure of a G alpha(i1)-peptide dimer., Johnston CA, Lobanova ES, Shavkunov AS, Low J, Ramer JK, Blaesius R, Fredericks Z, Willard FS, Kuhlman B, Arshavsky VY, Siderovski DP, Biochemistry. 2006 Sep 26;45(38):11390-400. PMID:16981699
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