Structure of translation factor eIF4E bound to m7GDP and interaction with 4E-binding protein.
eIF4E, the mRNA cap binding protein, is a master switch that controls eukaryotic translation. To be active, it must bind eIF4G and form the eIF4F complex, which also contains eIF4A. Translation is downregulated by association of eIF4E with 4E-BP, which occupies the eIF4G binding site. Signalling events acting on 4E-BP cause it to dissociate from eIF4E, and eIF4E is then free to bind eIF4G to form the active eIF4F complex. We have solved the structure of the yeast eIF4E/m7Gpp complex in a CHAPS micelle. We determined the position of the second nucleotide in a complex with m7GpppA, and identified the 4E-BP binding site. eIF4E has a curved eight-stranded antiparallel beta-sheet, decorated with three helices on the convex face and three smaller helices inserted in connecting loops. The m7G of the cap is intercalated into a stack of tryptophans in the concave face. The 4E-BP binding site is located in a region encompassing one edge of the beta-sheet, the adjacent helix a2 and several regions of non-regular secondary structure. It is adjacent to, but does not overlap the cap-binding site.
Matsuo
H
H
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachussetts 02115, USA.
Li
H
H
McGuire
A M
AM
Fletcher
C M
CM
Gingras
A C
AC
Sonenberg
N
N
Wagner
G
G
D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D002793:Cholic Acids; D003902:Detergents; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008823:Micelles; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000737:chemistry*; D011487:Protein Conformation; D012314:RNA Cap Analogs / Q000737:chemistry*; D014364:Tryptophan / Q000737:chemistry; D015003:Yeasts / Q000737:chemistry
D002352:Carrier Proteins; D002793:Cholic Acids; D003902:Detergents; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D008823:Micelles; D010448:Peptide Initiation Factors; D012314:RNA Cap Analogs; C111106:7-methylguanosine 5'-diphosphate; D006153:Guanosine Diphosphate; D014364:Tryptophan; C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate