Structural and biochemical studies of SLIP1-SLBP identify DBP5 and eIF3g as SLIP1-binding proteins
- Authors
- von Moeller, H., Lerner, R., Ricciardi, A., Basquin, C., Marzluff, W.F., and Conti, E.
- ID
- ZDB-PUB-130710-83
- Date
- 2013
- Source
- Nucleic acids research 41(16): 7960-71 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- DEAD-box RNA Helicases/chemistry*
- DEAD-box RNA Helicases/metabolism
- Eukaryotic Initiation Factor-3/chemistry
- Eukaryotic Initiation Factor-3/metabolism
- Humans
- Models, Molecular
- Molecular Sequence Data
- Nucleocytoplasmic Transport Proteins/chemistry*
- Nucleocytoplasmic Transport Proteins/metabolism
- Protein Interaction Domains and Motifs
- Protein Multimerization
- RNA-Binding Proteins/chemistry*
- RNA-Binding Proteins/metabolism
- Sequence Alignment
- Zebrafish Proteins/chemistry*
- Zebrafish Proteins/metabolism
- PubMed
- 23804756 Full text @ Nucleic Acids Res.
In metazoans, replication-dependent histone mRNAs end in a stem-loop structure instead of the poly(A) tail characteristic of all other mature mRNAs. This specialized 32 end is bound by stem-loop binding protein (SLBP), a protein that participates in the nuclear export and translation of histone mRNAs. The translational activity of SLBP is mediated by interaction with SLIP1, a middle domain of initiation factor 4G (MIF4G)-like protein that connects to translation initiation. We determined the 2.5 Å resolution crystal structure of zebrafish SLIP1 bound to the translation–activation domain of SLBP and identified the determinants of the recognition. We discovered a SLIP1-binding motif (SBM) in two additional proteins: the translation initiation factor eIF3g and the mRNA-export factor DBP5. We confirmed the binding of SLIP1 to DBP5 and eIF3g by pull-down assays and determined the 3.25 Å resolution structure of SLIP1 bound to the DBP5 SBM. The SBM-binding and homodimerization residues of SLIP1 are conserved in the MIF4G domain of CBP80/20-dependent translation initiation factor (CTIF). The results suggest how the SLIP1 homodimer or a SLIP1–CTIF heterodimer can function as platforms to bridge SLBP with SBM-containing proteins involved in different steps of mRNA metabolism.