1s9d
From Proteopedia
(New page: 200px<br /> <applet load="1s9d" size="450" color="white" frame="true" align="right" spinBox="true" caption="1s9d, resolution 1.80Å" /> '''ARF1[DELTA 1-17]-GD...) |
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| - | [[Image:1s9d.gif|left|200px]]<br /> | + | [[Image:1s9d.gif|left|200px]]<br /><applet load="1s9d" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1s9d" size=" | + | |
caption="1s9d, resolution 1.80Å" /> | caption="1s9d, resolution 1.80Å" /> | ||
'''ARF1[DELTA 1-17]-GDP-MG IN COMPLEX WITH BREFELDIN A AND A SEC7 DOMAIN'''<br /> | '''ARF1[DELTA 1-17]-GDP-MG IN COMPLEX WITH BREFELDIN A AND A SEC7 DOMAIN'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Small GTP-binding (G) proteins are activated by GDP/GTP nucleotide | + | Small GTP-binding (G) proteins are activated by GDP/GTP nucleotide exchange stimulated by guanine nucleotide exchange factors (GEFs). Nucleotide dissociation from small G protein-GEF complexes involves transient GDP-bound intermediates whose structures have never been described. In the case of Arf proteins, small G proteins that regulate membrane traffic in eukaryotic cells, such intermediates can be trapped either by the natural inhibitor brefeldin A or by charge reversal at the catalytic glutamate of the Sec7 domain of their GEFs. Here we report the crystal structures of these intermediates that show that membrane recruitment of Arf and nucleotide dissociation are separate reactions stimulated by Sec7. The reactions proceed through sequential rotations of the Arf.GDP core towards the Sec7 catalytic site, and are blocked by interfacial binding of brefeldin A and unproductive stabilization of GDP by charge reversal. The structural characteristics of the reaction and its modes of inhibition reveal unexplored ways in which to inhibit the activation of small G proteins. |
==About this Structure== | ==About this Structure== | ||
| - | 1S9D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG, GDP and AFB as [http://en.wikipedia.org/wiki/ligands ligands]. This structure | + | 1S9D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=GDP:'>GDP</scene> and <scene name='pdbligand=AFB:'>AFB</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1R8R. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S9D OCA]. |
==Reference== | ==Reference== | ||
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[[Category: protein transport/exchange factor]] | [[Category: protein transport/exchange factor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:59:12 2008'' |
Revision as of 12:59, 21 February 2008
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ARF1[DELTA 1-17]-GDP-MG IN COMPLEX WITH BREFELDIN A AND A SEC7 DOMAIN
Overview
Small GTP-binding (G) proteins are activated by GDP/GTP nucleotide exchange stimulated by guanine nucleotide exchange factors (GEFs). Nucleotide dissociation from small G protein-GEF complexes involves transient GDP-bound intermediates whose structures have never been described. In the case of Arf proteins, small G proteins that regulate membrane traffic in eukaryotic cells, such intermediates can be trapped either by the natural inhibitor brefeldin A or by charge reversal at the catalytic glutamate of the Sec7 domain of their GEFs. Here we report the crystal structures of these intermediates that show that membrane recruitment of Arf and nucleotide dissociation are separate reactions stimulated by Sec7. The reactions proceed through sequential rotations of the Arf.GDP core towards the Sec7 catalytic site, and are blocked by interfacial binding of brefeldin A and unproductive stabilization of GDP by charge reversal. The structural characteristics of the reaction and its modes of inhibition reveal unexplored ways in which to inhibit the activation of small G proteins.
About this Structure
1S9D is a Protein complex structure of sequences from Bos taurus and Homo sapiens with , and as ligands. This structure supersedes the now removed PDB entry 1R8R. Full crystallographic information is available from OCA.
Reference
Structural snapshots of the mechanism and inhibition of a guanine nucleotide exchange factor., Renault L, Guibert B, Cherfils J, Nature. 2003 Dec 4;426(6966):525-30. PMID:14654833
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