Structure of the exon junction core complex with a trapped DEAD-box ATPase bound to RNA.
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.
Andersen
Christian B F
CB
Department of Molecular Biology, University of Aarhus, DK-8000 Aarhus, Denmark.
Ballut
Lionel
L
Johansen
Jesper S
JS
Chamieh
Hala
H
Nielsen
Klaus H
KH
Oliveira
Cristiano L P
CL
Pedersen
Jan Skov
JS
Séraphin
Bertrand
B
Le Hir
Hervé
H
Andersen
Gregers Rom
GR
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D000266:Adenylyl Imidodiphosphate / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D053487:DEAD-box RNA Helicases; D019281:Dimerization; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism; D039601:Eukaryotic Initiation Factor-4A / Q000737:chemistry* / Q000378:metabolism; D005091:Exons; D006801:Humans; D006860:Hydrogen Bonding; D006868:Hydrolysis; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D011072:Poly U / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D020365:RNA Helicases / Q000737:chemistry / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism
C459802:CASC3 protein, human; D029721:Drosophila Proteins; C491494:MAGOH protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C406243:RBM8A protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000266:Adenylyl Imidodiphosphate; D011072:Poly U; D000255:Adenosine Triphosphate; D039601:Eukaryotic Initiation Factor-4A; C088269:vas protein, Drosophila; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases