Importance of C-terminal flexible region of 4E-binding protein in binding with eukaryotic initiation factor 4E.
Although the alpha-helical Y(X)4Lvarphi containing region of eIF4E-binding protein (4EBP) is the major binding region with eukaryotic initiation factor 4E (eIF4E), the roles of its N- and C-terminal regions in the binding are hardly known. To clarify the roles of these flexible regions in the interaction, the binding features of the sequentially N-, C-, or both-terminal-residue-deleted 4EBP2 mutants were investigated by surface plasmon resonance (SPR) analysis. It was shown that the C-terminal His74-Glu89 sequence has an auxiliary, but indispensable, function in stabilizing the binding to eIF4E. The possible interaction with eIF4E was estimated by molecular dynamics simulation. This is the first report on the importance of the C-terminal flexible region in the eIF4E-binding regulation of 4EBP.
Mizuno
Atsuo
A
Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
In
Yasuko
Y
Fujita
Yuki
Y
Abiko
Fumi
F
Miyagawa
Hiroo
H
Kitamura
Kunihiro
K
Tomoo
Koji
K
Ishida
Toshimasa
T
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005973:Glutamine / Q000235:genetics / Q000378:metabolism; D006639:Histidine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary
C104151:EIF4EBP2 protein, human; D039561:Eukaryotic Initiation Factor-4E; D039642:Eukaryotic Initiation Factors; D005973:Glutamine; D006639:Histidine