2gpq
From Proteopedia
(New page: 200px<br /> <applet load="2gpq" size="450" color="white" frame="true" align="right" spinBox="true" caption="2gpq" /> '''Cap-free structure of eIF4E suggests basis ...) |
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'''Cap-free structure of eIF4E suggests basis for its allosteric regulation'''<br /> | '''Cap-free structure of eIF4E suggests basis for its allosteric regulation'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The activity of the eukaryotic translation initiation factor eIF4E is | + | The activity of the eukaryotic translation initiation factor eIF4E is modulated through conformational response to its ligands. For example, eIF4G and eIF4E-binding proteins (4E-BPs) modulate cap affinity, and thus physiological activity of eIF4E, by binding a site distal to the 7-methylguanosine cap-binding site. Further, cap binding substantially modulates eIF4E's affinity for eIF4G and the 4E-BPs. To date, only cap-bound eIF4E structures were reported. In the absence of structural information on the apo form, the molecular underpinnings of this conformational response mechanism cannot be established. We report here the first cap-free eIF4E structure. Apo-eIF4E exhibits structural differences in the cap-binding site and dorsal surface relative to cap-eIF4E. Analysis of structure and dynamics of apo-eIF4E, and changes observed upon ligand binding, reveal a molecular basis for eIF4E's conformational response to these ligands. In particular, alterations in the S4-H4 loop, distal to either the cap or eIF4G binding sites, appear key to modulating these effects. Mutation in this loop mimics these effects. Overall, our studies have important implications for the regulation of eIF4E. |
==About this Structure== | ==About this Structure== | ||
| - | 2GPQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 2GPQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GPQ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Borden, K | + | [[Category: Borden, K L.B.]] |
| - | [[Category: Osborne, M | + | [[Category: Osborne, M J.]] |
[[Category: Volpon, L.]] | [[Category: Volpon, L.]] | ||
[[Category: apo form]] | [[Category: apo form]] | ||
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[[Category: translation regulation]] | [[Category: translation regulation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:34:01 2008'' |
Revision as of 15:34, 21 February 2008
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Cap-free structure of eIF4E suggests basis for its allosteric regulation
Overview
The activity of the eukaryotic translation initiation factor eIF4E is modulated through conformational response to its ligands. For example, eIF4G and eIF4E-binding proteins (4E-BPs) modulate cap affinity, and thus physiological activity of eIF4E, by binding a site distal to the 7-methylguanosine cap-binding site. Further, cap binding substantially modulates eIF4E's affinity for eIF4G and the 4E-BPs. To date, only cap-bound eIF4E structures were reported. In the absence of structural information on the apo form, the molecular underpinnings of this conformational response mechanism cannot be established. We report here the first cap-free eIF4E structure. Apo-eIF4E exhibits structural differences in the cap-binding site and dorsal surface relative to cap-eIF4E. Analysis of structure and dynamics of apo-eIF4E, and changes observed upon ligand binding, reveal a molecular basis for eIF4E's conformational response to these ligands. In particular, alterations in the S4-H4 loop, distal to either the cap or eIF4G binding sites, appear key to modulating these effects. Mutation in this loop mimics these effects. Overall, our studies have important implications for the regulation of eIF4E.
About this Structure
2GPQ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Cap-free structure of eIF4E suggests a basis for conformational regulation by its ligands., Volpon L, Osborne MJ, Topisirovic I, Siddiqui N, Borden KL, EMBO J. 2006 Nov 1;25(21):5138-49. Epub 2006 Oct 12. PMID:17036047
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