3m94

Complex crystal structure of Ascaris suum eIF4E-3 with m2,2,7G cap

spinqualitylabelsall models 3m94, resolution 2.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3m94 is a 2 chain structure with sequence from Ascaris suum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ACE, M7M Related: 3m93 Resources: FirstGlance, OCA, RCSB, PDBsum Function [4EBP1_HUMAN] Regulates eIF4E activity by preventing its assembly into the eIF4F complex. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways. Publication Abstract from PubMed Metazoan spliced leader (SL) trans-splicing generates mRNAs with an m(2,2,7)G-cap and a common downstream SL RNA sequence. The mechanism for eIF4E binding an m(2,2,7)G-cap is unknown. Here, we describe the first structure of an eIF4E with an m(2,2,7)G-cap and compare it to the cognate m(7)G-eIF4E complex. These structures and Nuclear Magnetic Resonance (NMR) data indicate that the nematode Ascaris suum eIF4E binds the two different caps in a similar manner except for the loss of a single hydrogen bond on binding the m(2,2,7)G-cap. Nematode and mammalian eIF4E both have a low affinity for m(2,2,7)G-cap compared with the m(7)G-cap. Nematode eIF4E binding to the m(7)G-cap, m(2,2,7)G-cap and the m(2,2,7)G-SL 22-nt RNA leads to distinct eIF4E conformational changes. Additional interactions occur between Ascaris eIF4E and the SL on binding the m(2,2,7)G-SL. We propose interactions between Ascaris eIF4E and the SL impact eIF4G and contribute to translation initiation, whereas these interactions do not occur when only the m(2,2,7)G-cap is present. These data have implications for the contribution of 5'-UTRs in mRNA translation and the function of different eIF4E isoforms. Structural basis for nematode eIF4E binding an m2,2,7G-Cap and its implications for translation initiation.,Liu W, Jankowska-Anyszka M, Piecyk K, Dickson L, Wallace A, Niedzwiecka A, Stepinski J, Stolarski R, Darzynkiewicz E, Kieft J, Zhao R, Jones DN, Davis RE Nucleic Acids Res. 2011 Sep 29. PMID:21965542 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Eukaryotic initiation factor

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