Abstract
In higher eukaryotes, a multiprotein exon junction complex is deposited on spliced messenger RNAs. The complex is organized around a stable core, which serves as a binding platform for numerous factors that influence messenger RNA function. Here, we present the crystal structure of a tetrameric exon junction core complex containing the DEAD-box adenosine triphosphatase (ATPase) eukaryotic initiation factor 4AIII (eIF4AIII) bound to an ATP analog, MAGOH, Y14, a fragment of MLN51, and a polyuracil mRNA mimic. eIF4AIII interacts with the phosphate-ribose backbone of six consecutive nucleotides and prevents part of the bound RNA from being double stranded. The MAGOH and Y14 subunits lock eIF4AIII in a prehydrolysis state, and activation of the ATPase probably requires only modest conformational changes in eIF4AIII motif I.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphate / analogs & derivatives
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Adenosine Triphosphate / metabolism
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Adenylyl Imidodiphosphate / metabolism
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Crystallography, X-Ray
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DEAD-box RNA Helicases
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Dimerization
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Drosophila Proteins / chemistry
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Drosophila Proteins / metabolism
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Eukaryotic Initiation Factor-4A / chemistry*
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Eukaryotic Initiation Factor-4A / metabolism
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Exons*
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Humans
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Hydrogen Bonding
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Hydrolysis
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Models, Molecular
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Molecular Sequence Data
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Mutation
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Neoplasm Proteins / chemistry*
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Neoplasm Proteins / metabolism
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Nuclear Proteins / chemistry*
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Nuclear Proteins / metabolism
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Nucleic Acid Conformation
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Poly U / chemistry*
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Poly U / metabolism
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Protein Conformation
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Protein Structure, Secondary
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Protein Structure, Tertiary
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RNA Helicases / chemistry
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RNA Helicases / metabolism
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RNA, Messenger / chemistry*
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RNA, Messenger / metabolism
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RNA-Binding Proteins / chemistry*
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RNA-Binding Proteins / metabolism
Substances
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CASC3 protein, human
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Drosophila Proteins
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MAGOH protein, human
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Neoplasm Proteins
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Nuclear Proteins
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RBM8A protein, human
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RNA, Messenger
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RNA-Binding Proteins
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Adenylyl Imidodiphosphate
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Poly U
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Adenosine Triphosphate
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Eukaryotic Initiation Factor-4A
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vas protein, Drosophila
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DEAD-box RNA Helicases
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RNA Helicases