Cocrystal structure of the messenger RNA 5' cap-binding protein (eIF4E) bound to 7-methyl-GDP.
The X-ray structure of the eukaryotic translation initiation factor 4E (eIF4E), bound to 7-methyl-GDP, has been determined at 2.2 A resolution. eIF4E recognizes 5' 7-methyl-G(5')ppp(5')N mRNA caps during the rate-limiting initiation step of translation. The protein resembles a cupped hand and consists of a curved, 8-stranded antiparallel beta sheet, backed by three long alpha helices. 7-methyl-GDP binds in a narrow cap-binding slot on the molecule's concave surface, where 7-methyl-guanine recognition is mediated by base sandwiching between two conserved tryptophans, plus formation of three hydrogen bonds and a van der Waals contact between its N7-methyl group and a third conserved tryptophan. The convex dorsal surface of the molecule displays a phylogenetically conserved hydrophobic/acidic portion, which may interact with other translation initiation factors and regulatory proteins.
Marcotrigiano
J
J
Laboratories of Molecular Biophysics, The Rockefeller University, New York, New York 10021, USA.
Gingras
A C
AC
Sonenberg
N
N
Burley
S K
SK
D001665:Binding Sites / Q000502:physiology; D017124:Conserved Sequence; D003461:Crystallography; D004926:Escherichia coli / Q000235:genetics; D005057:Eukaryotic Cells / Q000502:physiology; D039561:Eukaryotic Initiation Factor-4E; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000378:metabolism; D008745:Methylation; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010448:Peptide Initiation Factors / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000502:physiology; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012314:RNA Cap Analogs / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D039561:Eukaryotic Initiation Factor-4E; D010448:Peptide Initiation Factors; D012314:RNA Cap Analogs; D012333:RNA, Messenger; C111106:7-methylguanosine 5'-diphosphate; D006153:Guanosine Diphosphate