PDBsum entry 3zhe

mRNA-binding protein

PDB id: 3zhe

Contents

Protein chains

399 a.a.

390 a.a.

PDB id:

3zhe

Name:

mRNA-binding protein

Title:

Structure of thE C. Elegans smg5-smg7 complex

Structure:

Nonsense-mediated mRNA decay protein. Chain: a, c. Fragment: 14-3-3 and alpha-helical domains, residues 1-420. Synonym: protein smg-5. Engineered: yes. Protein smg-7. Chain: b, d. Fragment: 14-3-3 and alpha-helical domains, residues 1-395. Engineered: yes

Source:

Caenorhabditis elegans. Organism_taxid: 6239. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: star.

Resolution:

3.00Å R-factor: 0.223 R-free: 0.249

Authors:

S.Jonas,O.Weichenrieder,E.Izaurralde

Key ref:

S.Jonas et al. (2013). An unusual arrangement of two 14-3-3-like domains in the SMG5-SMG7 heterodimer is required for efficient nonsense-mediated mRNA decay. Genes Dev, 27, 211-225. PubMed id: 23348841

Date:

21-Dec-12 Release date: 06-Feb-13

Protein chains

G5ECF1  (G5ECF1_CAEEL) -  Nonsense-mediated mRNA decay protein from Caenorhabditis elegans

Seq: 549 a.a.

Struc: 399 a.a.

Protein chains

G5EF47  (G5EF47_CAEEL) -  DNA/RNA-binding domain-containing protein from Caenorhabditis elegans

Seq: 458 a.a.

Struc: 390 a.a.

Genes Dev 27:211-225 (2013)

PubMed id: 23348841

An unusual arrangement of two 14-3-3-like domains in the SMG5-SMG7 heterodimer is required for efficient nonsense-mediated mRNA decay.

S.Jonas, O.Weichenrieder, E.Izaurralde.

ABSTRACT

The nonsense-mediated mRNA decay (NMD) pathway triggers the rapid degradation of aberrant mRNAs containing premature translation termination codons (PTCs). In metazoans, NMD requires three 14-3-3-like proteins: SMG5, SMG6, and SMG7. These proteins are recruited to PTC-containing mRNAs through the interaction of their 14-3-3-like domains with phosphorylated UPF1, the central NMD effector. Recruitment of SMG5, SMG6, and SMG7 causes NMD target degradation. In this study, we report the crystal structure of the Caenorhabditis elegans SMG5-SMG7 complex. The 14-3-3-like phosphopeptide recognition domains of SMG5 and SMG7 heterodimerize in an unusual perpendicular back-to-back orientation in which the peptide-binding sites face opposite directions. Structure-based mutants and functional assays indicate that the SMG5-SMG7 interaction is conserved and is crucial for efficient NMD in human cells. Notably, we demonstrate that heterodimerization increases the affinity of the SMG5-SMG7 complex for UPF1. Furthermore, we show that the degradative activity of the SMG5-SMG7 complex resides in SMG7 and that the SMG5-SMG7 complex and SMG6 play partially redundant roles in the degradation of aberrant mRNAs. We propose that the SMG5-SMG7 complex binds to phosphorylated UPF1 with high affinity and recruits decay factors to the mRNA target through SMG7, thus promoting target degradation.