Molecular architecture of LSM14 interactions involved in the assembly of mRNA silencing complexes.

The LSM domain-containing protein LSM14/Rap55 plays a role in mRNA decapping, translational repression, and RNA granule (P-body) assembly. How LSM14 interacts with the mRNA silencing machinery, including the eIF4E-binding protein 4E-T and the DEAD-box helicase DDX6, is poorly understood. Here we report the crystal structure of the LSM domain of ...
LSM14 bound to a highly conserved C-terminal fragment of 4E-T. The 4E-T C-terminus forms a bi-partite motif that wraps around the N-terminal LSM domain of LSM14. We also determined the crystal structure of LSM14 bound to the C-terminal RecA-like domain of DDX6. LSM14 binds DDX6 via a unique non-contiguous motif with distinct directionality as compared to other DDX6-interacting proteins. Together with mutational and proteomic studies, the LSM14-DDX6 structure reveals that LSM14 has adopted a divergent mode of binding DDX6 in order to support the formation of mRNA silencing complexes and P-body assembly.
Mesh Terms:
Amino Acid Sequence, Animals, Binding Sites, Caenorhabditis elegans, Crystallography, X-Ray, DEAD-box RNA Helicases, Drosophila melanogaster, Eukaryotic Initiation Factor-4E, HeLa Cells, Humans, Hydrophobic and Hydrophilic Interactions, Models, Molecular, Mutation, Protein Binding, Protein Conformation, Protein Interaction Domains and Motifs, Protein Structure, Secondary, Proteins, Proteomics, Proto-Oncogene Proteins, RNA Interference, RNA, Messenger, Rec A Recombinases, Recombinant Proteins, Ribonucleoproteins, Sequence Alignment
EMBO J.
Date: Dec. 03, 2017
Download Curated Data For This Publication
218273
Switch View:
  • Interactions 29