3AM7

Crystal structure of the ternary complex of eIF4E-M7GTP-4EBP2 peptide

Summary for 3AM7

• Entry DOI: 10.2210/pdb3am7/pdb
• Related: 1WKW
• Descriptor: Eukaryotic translation initiation factor 4E, Eukaryotic translation initiation factor 4E-binding protein 2, 7-METHYL-GUANOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: cap, translation, protein-protein complex, translation-protein binding complex, translation/protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 25109.09

Authors

Tomoo, K.,Fukuyo, A.,In, Y.,Ishida, T. (deposition date: 2010-08-17, release date: 2011-08-17, Last modification date: 2024-05-29)

Primary citation

Fukuyo, A.,In, Y.,Ishida, T.,Tomoo, K.
Structural scaffold for eIF4E binding selectivity of 4E-BP isoforms: crystal structure of eIF4E binding region of 4E-BP2 and its comparison with that of 4E-BP1.
J.Pept.Sci., 17:650-657, 2011

PubMed Abstract: To clarify the higher eukaryotic initiation factor 4E (eIF4E) binding selectivity of 4E-binding protein 2 (4E-BP2) than of 4E-BP1, as determined by Trp fluorescence analysis, the crystal structure of the eIF4E binding region of 4E-BP2 in complex with m(7) GTP-bound human eIF4E has been determined by X-ray diffraction analysis and compared with that of 4E-BP1. The crystal structure revealed that the Pro47-Ser65 moiety of 4E-BP2 adopts a L-shaped conformation involving extended and α-helical structures and extends over the N-terminal loop and two different helix regions of eIF4E through hydrogen bonds, and electrostatic and hydrophobic interactions; these features were similarly observed for 4E-BP1. Although the pattern of the overall interaction of 4E-BP2 with eIF4E was similar to that of 4E-BP1, a notable difference was observed for the 60-63 sequence in relation to the conformation and binding selectivity of the 4E-BP isoform, i.e. Met-Glu-Cys-Arg for 4E-BP1 and Leu-Asp-Arg-Arg for 4E-BP2. In this paper, we report that the structural scaffold of the eIF4E binding preference for 4E-BP2 over 4E-BP1 is based on the stacking of the Arg63 planar side chain on the Trp73 indole ring of eIF4E and the construction of a compact hydrophobic space around the Trp73 indole ring by the Leu59-Leu60 sequence of 4E-BP2.

PubMed: 21661078
DOI: 10.1002/psc.1384

Experimental method

X-RAY DIFFRACTION (2.2 Å)