Structure of the exon junction core complex with a trapped DEAD-box ATPase bound to RNA

Science. 2006 Sep 29;313(5795):1968-72. doi: 10.1126/science.1131981. Epub 2006 Aug 24.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analogs & derivatives
  • Adenosine Triphosphate / metabolism
  • Adenylyl Imidodiphosphate / metabolism
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • DEAD-box RNA Helicases
  • Dimerization
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism
  • Eukaryotic Initiation Factor-4A / chemistry*
  • Eukaryotic Initiation Factor-4A / metabolism
  • Exons*
  • Humans
  • Hydrogen Bonding
  • Hydrolysis
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Neoplasm Proteins / chemistry*
  • Neoplasm Proteins / metabolism
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / metabolism
  • Nucleic Acid Conformation
  • Poly U / chemistry*
  • Poly U / metabolism
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA Helicases / chemistry
  • RNA Helicases / metabolism
  • RNA, Messenger / chemistry*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / metabolism

Substances

  • CASC3 protein, human
  • Drosophila Proteins
  • MAGOH protein, human
  • Neoplasm Proteins
  • Nuclear Proteins
  • RBM8A protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • Adenylyl Imidodiphosphate
  • Poly U
  • Adenosine Triphosphate
  • Eukaryotic Initiation Factor-4A
  • vas protein, Drosophila
  • DEAD-box RNA Helicases
  • RNA Helicases

Associated data

  • PDB/2HXY
  • PDB/2HYI