The crystal structures of the full-length human eukaryotic initiation factor 
(eIF) 4E complexed with two mRNA cap analogues [7-methylguanosine 
5'-triphosphate (m(7)GTP) and 
P(1)-7-methylguanosine-P(3)-adenosine-5',5'-triphosphate (m(7)GpppA)] were 
determined at 2.0 A resolution (where 1 A=0.1 nm). The flexibility of the 
C-terminal loop region of eIF4E complexed with m(7)GTP was significantly reduced 
when complexed with m(7)GpppA, suggesting the importance of the second 
nucleotide in the mRNA cap structure for the biological function of eIF4E, 
especially the fixation and orientation of the C-terminal loop region, including 
the eIF4E phosphorylation residue. The present results provide the structural 
basis for the biological function of both N- and C-terminal mobile regions of 
eIF4E in translation initiation, especially the regulatory function through the 
switch-on/off of eIF4E-binding protein-eIF4E phosphorylation.