Distinct Features of Cap Binding by eIF4E1b Proteins
PBN-AR
Instytucja
Centrum Nowych Technologii UW (Uniwersytet Warszawski)
Informacje podstawowe
Główny język publikacji
en
Czasopismo
JOURNAL OF MOLECULAR BIOLOGY
ISSN
0022-2836
EISSN
Wydawca
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI
URL
Rok publikacji
2015
Numer zeszytu
2
Strony od-do
387-405
Numer tomu
427
Identyfikator DOI
Liczba arkuszy
Autorzy
(liczba autorów: 6)
Pozostali autorzy
+ 5
Słowa kluczowe
en
eukaryotic
initiation factor eIF4E1b
translational repression
binding affinity
Xenopus laevis
Streszczenia
Język
en
Treść
Abstract eIF4E1b, closely related to the canonical translation initiation factor 4E (eIF4E1a), cap-binding protein is highly expressed in mouse, Xenopus and zebrafish oocytes. We have previously characterized eIF4E1b as a component of the CPEB mRNP translation repressor complex along with the eIF4E-binding protein 4E-Transporter, the Xp54/DDX6 RNA helicase and additional RNA-binding proteins. eIF4E1b exhibited only very weak interactions with m7GTP-Sepharose and, rather than binding eIF4G, interacted with 4E-T. Here we undertook a detailed examination of both Xenopus and human eIF4E1b interactions with cap analogues using fluorescence titration and homology modeling. The predicted structure of eIF4E1b maintains the α + β fold characteristic of eIF4E proteins and its cap-binding pocket is similarly arranged by critical amino acids: Trp56, Trp102, Glu103, Trp166, Arg112, Arg157 and Lys162 and residues of the C-terminal loop. However, we demonstrate that eIF4E1b is 3-fold less well able to bind the cap than eIF4E1a, both proteins being highly stimulated by methylation at N7 of guanine. Moreover, eIF4E1b proteins are distinguishable from eIF4E1a by a set of conserved amino acid substitutions, several of which are located near to cap-binding residues. Indeed, eIF4E1b possesses several distinct features, namely, enhancement of cap binding by a benzyl group at N7 position of guanine, a reduced response to increasing length of the phosphate chain and increased binding to a cap separated by a linker from Sepharose, suggesting differences in the arrangement of the protein's core. In agreement, mutagenesis of the amino acids differentiating eIF4E1b from eIF4E1a reduces cap binding by eIF4E1a 2-fold, demonstrating their role in modulating cap binding.
Cechy publikacji
ORIGINAL_ARTICLE
Inne
System-identifier
604064
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