6L53

Structure of SMG1

Summary for 6L53

• Entry DOI: 10.2210/pdb6l53/pdb
• EMDB information: 0836
• Descriptor: Serine/threonine-protein kinase SMG1 (1 entity in total)
• Functional Keywords: smg1, cryo-em, nonsense-mediated mrna decay, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 410966.97

Authors

Xu, Y.,Qi, Y. (deposition date: 2019-10-22, release date: 2020-04-15, Last modification date: 2024-03-27)

Primary citation

Zhu, L.,Li, L.,Qi, Y.,Yu, Z.,Xu, Y.
Cryo-EM structure of SMG1-SMG8-SMG9 complex.
Cell Res., 29:1027-1034, 2019

PubMed Abstract: 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.

PubMed: 31729466
DOI: 10.1038/s41422-019-0255-3

Experimental method

ELECTRON MICROSCOPY (3.63 Å)