4B6U
Solution structure of eIF4E3 in complex with m7GDP
Summary for 4B6U
| Entry DOI | 10.2210/pdb4b6u/pdb |
| Related | 4B6V |
| NMR Information | BMRB: 18667 |
| Descriptor | EUKARYOTIC TRANSLATION INITIATION FACTOR 4E TYPE 3, 7N-METHYL-8-HYDROGUANOSINE-5'-DIPHOSPHATE (2 entities in total) |
| Functional Keywords | translation |
| Biological source | MUS MUSCULUS (HOUSE MOUSE) |
| Total number of polymer chains | 1 |
| Total formula weight | 23322.31 |
| Authors | Osborne, M.J.,Volpon, L.,Kornblatt, J.A.,Culkjovic-Kraljcic, B.,Baguet, A.,Borden, K.L.B. (deposition date: 2012-08-15, release date: 2013-03-06, Last modification date: 2024-06-19) |
| Primary citation | Osborne, M.J.,Volpon, L.,Kornblatt, J.A.,Culjkovic-Kraljcic, B.,Baguet, A.,Borden, K.L.B. Eif4E3 Acts as a Tumor Suppressor by Utilizing an Atypical Mode of Methyl-7-Guanosine CAP Recognition Proc.Natl.Acad.Sci.USA, 110:3877-, 2013 Cited by PubMed Abstract: Recognition of the methyl-7-guanosine (m(7)G) cap structure on mRNA is an essential feature of mRNA metabolism and thus gene expression. Eukaryotic translation initiation factor 4E (eIF4E) promotes translation, mRNA export, proliferation, and oncogenic transformation dependent on this cap-binding activity. eIF4E-cap recognition is mediated via complementary charge interactions of the positively charged m(7)G cap between the negative π-electron clouds from two aromatic residues. Here, we demonstrate that a variant subfamily, eIF4E3, specifically binds the m(7)G cap in the absence of an aromatic sandwich, using instead a different spatial arrangement of residues to provide the necessary electrostatic and van der Waals contacts. Contacts are much more extensive between eIF4E3-cap than other family members. Structural analyses of other cap-binding proteins indicate this recognition mode is atypical. We demonstrate that eIF4E3 relies on this cap-binding activity to act as a tumor suppressor, competing with the growth-promoting functions of eIF4E. In fact, reduced eIF4E3 in high eIF4E cancers suggests that eIF4E3 underlies a clinically relevant inhibitory mechanism that is lost in some malignancies. Taken together, there is more structural plasticity in cap recognition than previously thought, and this is physiologically relevant. PubMed: 23431134DOI: 10.1073/PNAS.1216862110 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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