Distinct Features of Cap Binding by eIF4E1b Proteins
PBN-AR
Instytucja
Wydział Fizyki (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
Link do pełnego tekstu
Identyfikator DOI
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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
discipline:Biofizyka – dziedzina nauk fizycznych
discipline:Biophysics – field of physical sciences
Original article
Original article presents the results of original research or experiment.
Oryginalny artykuł naukowy
Oryginalny artykuł naukowy przedstawia rezultaty oryginalnych badań naukowych lub eksperymentu.
Inne
System-identifier
PBN-R:604064
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