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A conserved motif within the flexible C-terminus of the translational regulator 4E-BP is required for tight binding to the mRNA cap-binding protein eIF4E.
Paku, Keum Soon; Umenaga, Yu; Usui, Tsunego; Fukuyo, Ai; Mizuno, Atsuo; In, Yasuko; Ishida, Toshimasa; Tomoo, Koji.
Afiliação
  • Paku KS; Department of Physical Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
Biochem J ; 441(1): 237-45, 2012 Jan 01.
Article em En | MEDLINE | ID: mdl-21913890
Although the central α-helical Y(X)4LΦ motif (X, variable amino acid; Φ, hydrophobic amino acid) of the translational regulator 4E-BP [eIF (eukaryotic initiation factor) 4E-binding protein] is the core binding region for the mRNA cap-binding protein eIF4E, the functions of its N- and C-terminal flexible regions for interaction with eIF4E remain to be elucidated. To identify the role for the C-terminal region in such an interaction, the binding features of full-length and sequential C-terminal deletion mutants of 4E-BPn (n=1-3) subtypes were investigated by SPR (surface plasmon resonance) analysis and ITC (isothermal titration calorimetry). Consequently, the conserved PGVTS/T motif within the C-terminal region was shown to act as the second binding region and to play an important role in the tight binding to eIF4E. The 4E-BP subtypes increased the association constant with eIF4E by approximately 1000-fold in the presence of this conserved region compared with that in the absence of this region. The sequential deletion of this conserved region in 4E-BP1 showed that deletion of Val81 leads to a considerable decrease in the binding ability of 4E-BP. Molecular dynamics simulation suggested that the conserved PGVTS/T region functions as a kind of paste, adhering the root of both the eIF4E N-terminal and 4E-BP C-terminal flexible regions through a hydrophobic interaction, where valine is located at the crossing position of both flexible regions. It is concluded that the conserved PGVTS/T motif within the flexible C-terminus of 4E-BP plays an auxiliary, but indispensable, role in strengthening the binding of eIF4E to the core Y(X)4LΦ motif.
Assuntos

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND Base de dados: MEDLINE Assunto principal: RNA Mensageiro / Fator de Iniciação 4E em Eucariotos / Fatores de Iniciação em Eucariotos Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Biochem J Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Contexto em Saúde: 3_ND Base de dados: MEDLINE Assunto principal: RNA Mensageiro / Fator de Iniciação 4E em Eucariotos / Fatores de Iniciação em Eucariotos Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Biochem J Ano de publicação: 2012 Tipo de documento: Article