elF4B and elF4G Jointly Stimulate elF4A ATPase and Unwinding Activities by Modulation of the elF4A Conformational Cycle

被引:52
作者
Andreou, Alexandra Zoi [1 ]
Klostermeier, Dagmar [1 ]
机构
[1] Univ Munster, Inst Phys Chem, D-48149 Munster, Germany
基金
瑞士国家科学基金会;
关键词
elF4A; DEAD-box helicase; ATP hydrolysis; conformational change; regulation; EUKARYOTIC TRANSLATION INITIATION; RNA HELICASE ACTIVITY; BOX PROTEIN EIF4A; MAMMALIAN TRANSLATION; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; BINDING; COMPLEX; MECHANISM; REVEALS;
D O I
10.1016/j.jmb.2013.09.027
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Eukaryotic translation initiation factor 4A (eIF4A) is a DEAD-box protein that participates in translation initiation. As an ATP-dependent RNA helicase, it is thought to resolve secondary structure elements from the 5 '-untranslated region of mRNAs to enable ribosome scanning. The RNA-stimulated ATPase and ATP-dependent helicase activities of elF4A are enhanced by auxiliary proteins, but the underlying mechanisms are still largely unknown. Here, we have dissected the effect of elF4B and elF4G on elF4A RNA-dependent ATPase- and RNA helicase activities and on elF4A conformation. We show for the first time that yeast elF4B, like its mammalian counterpart, can stimulate RNA unwinding by elF4A, although it does not affect the elF4A conformation. The elF4G middle domain enhances this stimulatory effect and promotes the formation of a closed elF4A conformation in the presence of ATP and RNA. The closed state of elF4A has been inferred but has not been observed experimentally before. elF4B and elF4G jointly stimulate ATP hydrolysis and RNA unwinding by elF4A and favor the formation of the closed elF4A conformer. Our results reveal distinct functions of elF4B and elF4G in synergistically stimulating the elF4A helicase activity in the mRNA scanning process. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:51 / 61
页数:11
相关论文
共 51 条
  • [1] Bypassing of stems versus linear base-by-base inspection of mammalian mRNAs during ribosomal scanning
    Abaeva, Irina S.
    Marintchev, Assen
    Pisareva, Vera P.
    Hellen, Christopher U. T.
    Pestova, Tatyana V.
    [J]. EMBO JOURNAL, 2011, 30 (01) : 115 - 129
  • [2] A SACCHAROMYCES-CEREVISIAE HOMOLOG OF MAMMALIAN TRANSLATION INITIATION FACTOR-4B CONTRIBUTES TO RNA HELICASE ACTIVITY
    ALTMANN, M
    MULLER, PP
    WITTMER, B
    RUCHTI, F
    LANKER, S
    TRACHSEL, H
    [J]. EMBO JOURNAL, 1993, 12 (10) : 3997 - 4003
  • [3] THE SACCHAROMYCES-CEREVISIAE TRANSLATION INITIATION-FACTOR TIF3 AND ITS MAMMALIAN HOMOLOG, ELF-4B, HAVE RNA ANNEALING ACTIVITY
    ALTMANN, M
    WITTMER, B
    METHOT, N
    SONENBERG, N
    TRACHSEL, H
    [J]. EMBO JOURNAL, 1995, 14 (15) : 3820 - 3827
  • [4] Structure of the exon junction core complex with a trapped DEAD-box ATPase bound to RNA
    Andersen, Christian B. F.
    Ballut, Lionel
    Johansen, Jesper S.
    Chamieh, Hala
    Nielsen, Klaus H.
    Oliveira, Cristiano L. P.
    Pedersen, Jan Skov
    Seraphin, Bertrand
    Le Hir, Herve
    Andersen, Gregers Rom
    [J]. SCIENCE, 2006, 313 (5795) : 1968 - 1972
  • [5] The DEAD-box helicase eIF4A Paradigm or the odd one out?
    Andreou, Alexandra Z.
    Klostermeier, Dagmar
    [J]. RNA BIOLOGY, 2013, 10 (01) : 19 - 32
  • [6] CONFORMATIONAL CHANGES OF DEAD-BOX HELICASES MONITORED BY SINGLE MOLECULE FLUORESCENCE RESONANCE ENERGY TRANSFER
    Andreou, Alexandra Z.
    Klostermeier, Dagmar
    [J]. RNA HELICASES, 2012, 511 : 75 - 109
  • [7] The DEAD Box Helicase YxiN Maintains a Closed Conformation during ATP Hydrolysis
    Aregger, Regula
    Klostermeier, Dagmar
    [J]. BIOCHEMISTRY, 2009, 48 (45) : 10679 - 10681
  • [8] The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling
    Arnold, K
    Bordoli, L
    Kopp, J
    Schwede, T
    [J]. BIOINFORMATICS, 2006, 22 (02) : 195 - 201
  • [9] RNA-binding activity of translation initiation factor eIF4G1 from Saccharomyces cerevisiae
    Berset, C
    Zurbriggen, A
    Djafarzadeh, S
    Altmann, M
    Trachsel, H
    [J]. RNA, 2003, 9 (07) : 871 - 880
  • [10] Wheat germ poly(A)-binding protein increases the ATPase and the RNA helicase activity of translation initiation factors eIF4A, eIF4B, and eIF-iso4F
    Bi, XP
    Goss, DJ
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (23) : 17740 - 17746