First time at Proteopedia? Click on the green links: they change the 3D image. Click and drag the molecules. Proteopedia is a 3D, interactive encyclopedia of proteins, RNA, DNA and other molecules. With a free user account, you can edit pages in Proteopedia. Visit the Main Page to learn more.
2gpq
From Proteopedia
| 2gpq, 10 NMR models () | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Domains: | IF4E | ||||||||
| |||||||||
| |||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
Cap-free structure of eIF4E suggests basis for its allosteric regulation
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.
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
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2GPQ is a 1 chain structure of sequence from Homo sapiens. Full experimental information is available from OCA.
Reference
- Volpon L, Osborne MJ, Topisirovic I, Siddiqui N, Borden KL. Cap-free structure of eIF4E suggests a basis for conformational regulation by its ligands. EMBO J. 2006 Nov 1;25(21):5138-49. Epub 2006 Oct 12. PMID:17036047
Page seeded by OCA on Mon Feb 16 20:45:49 2009
