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TitleCryo-EM structure of SMG1-SMG8-SMG9 complex.
Journal, issue, pagesCell Res, Vol. 29, Issue 12, Page 1027-1034, Year 2019
Publish dateNov 15, 2019
AuthorsLi Zhu / Liang Li / Yilun Qi / Zishuo Yu / Yanhui Xu /
PubMed AbstractNonsense-mediated mRNA decay (NMD) targets premature stop codon (PTC)-containing mRNAs for rapid degradation, and is essential for mammalian embryonic development, brain development and modulation of ...Nonsense-mediated mRNA decay (NMD) targets premature stop codon (PTC)-containing mRNAs for rapid degradation, and is essential for mammalian embryonic development, brain development and modulation of the stress response. The key event in NMD is the SMG1-mediated phosphorylation of an RNA helicase UPF1 and SMG1 kinase activity is inhibited by SMG8 and SMG9 in an unknown mechanism. Here, we determined the cryo-EM structures of human SMG1 at 3.6 Å resolution and the SMG1-SMG8-SMG9 complex at 3.4 Å resolution, respectively. SMG8 has a C-terminal kinase inhibitory domain (KID), which covers the catalytic pocket and inhibits the kinase activity of SMG1. Structural analyses suggest that GTP hydrolysis of SMG9 would lead to a dramatic conformational change of SMG8-SMG9 and the KID would move away from the inhibitory position to restore SMG1 kinase activity. Thus, our structural and biochemical analyses provide a mechanistic understanding of SMG1-SMG8-SMG9 complex assembly and the regulatory mechanism of SMG1 kinase activity.
External linksCell Res / PubMed:31729466 / PubMed Central
MethodsEM (single particle)
Resolution3.43 - 3.63 Å
Structure data

0836

6l53

EMDB-0836, PDB-6l53:
Structure of SMG1
Method: EM (single particle) / Resolution: 3.63 Å

0837

6l54

EMDB-0837: SMG189
PDB-6l54: Structure of SMG189
Method: EM (single particle) / Resolution: 3.43 Å

Chemicals

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM / Guanosine triphosphate

ChemComp-MG:
Unknown entry

Source
  • homo sapiens (human)
KeywordsTRANSFERASE / SMG1 / Cryo-EM / Nonsense-mediated mRNA decay / TRANSFERASE/TRANSCRIPTION / SMG189 / TRANSFERASE-TRANSCRIPTION complex

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