2nsz
From Proteopedia
(New page: 200px<br /><applet load="2nsz" size="450" color="white" frame="true" align="right" spinBox="true" caption="2nsz, resolution 1.15Å" /> '''1.15 Angstrom Crysta...) |
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| - | [[Image:2nsz.gif|left|200px]]<br /><applet load="2nsz" size=" | + | [[Image:2nsz.gif|left|200px]]<br /><applet load="2nsz" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2nsz, resolution 1.15Å" /> | caption="2nsz, resolution 1.15Å" /> | ||
'''1.15 Angstrom Crystal Structure of the MA3 domain of Pdcd4'''<br /> | '''1.15 Angstrom Crystal Structure of the MA3 domain of Pdcd4'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The tumor suppressor function of Programmed Cell Death 4 (Pdcd4) is | + | The tumor suppressor function of Programmed Cell Death 4 (Pdcd4) is achieved through interactions between Pdcd4 and components of the translation initiation complex, namely, the RNA helicase eIF4A and the scaffolding protein eIF4G. These interactions are mediated through two MA3 domains on the Pdcd4 molecule and result in inhibition of protein synthesis. We have solved the high-resolution crystal structure of the C-terminal MA3 (cMA3) domain of Pdcd4 in several crystal forms and demonstrated its similarity to the MA3 domain of eIF4G. As predicted by the structure, the cMA3 domain competes with eIF4Gc for binding to eIF4A and surprisingly is sufficient to inhibit translation initiation. Mutations that abolish eIF4A binding negate both functions of the cMA3. Interestingly mutations in the Akt phosphorylation site influenced neither cMA3 binding to eIF4A nor its ability to inhibit translation initiation. Finally, our structural analysis reveals MA3 domains to be a novel subfamily of VHS domains. |
==About this Structure== | ==About this Structure== | ||
| - | 2NSZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with SO4 and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2NSZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NSZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: tumor suppressor]] | [[Category: tumor suppressor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:10:36 2008'' |
Revision as of 16:10, 21 February 2008
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1.15 Angstrom Crystal Structure of the MA3 domain of Pdcd4
Overview
The tumor suppressor function of Programmed Cell Death 4 (Pdcd4) is achieved through interactions between Pdcd4 and components of the translation initiation complex, namely, the RNA helicase eIF4A and the scaffolding protein eIF4G. These interactions are mediated through two MA3 domains on the Pdcd4 molecule and result in inhibition of protein synthesis. We have solved the high-resolution crystal structure of the C-terminal MA3 (cMA3) domain of Pdcd4 in several crystal forms and demonstrated its similarity to the MA3 domain of eIF4G. As predicted by the structure, the cMA3 domain competes with eIF4Gc for binding to eIF4A and surprisingly is sufficient to inhibit translation initiation. Mutations that abolish eIF4A binding negate both functions of the cMA3. Interestingly mutations in the Akt phosphorylation site influenced neither cMA3 binding to eIF4A nor its ability to inhibit translation initiation. Finally, our structural analysis reveals MA3 domains to be a novel subfamily of VHS domains.
About this Structure
2NSZ is a Single protein structure of sequence from Mus musculus with and as ligands. Full crystallographic information is available from OCA.
Reference
Structural basis for inhibition of translation by the tumor suppressor Pdcd4., LaRonde-LeBlanc N, Santhanam AN, Baker AR, Wlodawer A, Colburn NH, Mol Cell Biol. 2007 Jan;27(1):147-56. Epub 2006 Oct 23. PMID:17060447
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