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-Structure paper
タイトル | A network of SMG-8, SMG-9 and SMG-1 C-terminal insertion domain regulates UPF1 substrate recruitment and phosphorylation. |
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ジャーナル・号・ページ | Nucleic Acids Res, Vol. 43, Issue 15, Page 7600-7611, Year 2015 |
掲載日 | 2015年9月3日 |
著者 | Aurélien Deniaud / Manikandan Karuppasamy / Thomas Bock / Simonas Masiulis / Karine Huard / Frédéric Garzoni / Kathrin Kerschgens / Matthias W Hentze / Andreas E Kulozik / Martin Beck / Gabriele Neu-Yilik / Christiane Schaffitzel / |
PubMed 要旨 | Mammalian nonsense-mediated mRNA decay (NMD) is a eukaryotic surveillance mechanism that degrades mRNAs containing premature translation termination codons. Phosphorylation of the essential NMD ...Mammalian nonsense-mediated mRNA decay (NMD) is a eukaryotic surveillance mechanism that degrades mRNAs containing premature translation termination codons. Phosphorylation of the essential NMD effector UPF1 by the phosphoinositide-3-kinase-like kinase (PIKK) SMG-1 is a key step in NMD and occurs when SMG-1, its two regulatory factors SMG-8 and SMG-9, and UPF1 form a complex at a terminating ribosome. Electron cryo-microscopy of the SMG-1-8-9-UPF1 complex shows the head and arm architecture characteristic of PIKKs and reveals different states of UPF1 docking. UPF1 is recruited to the SMG-1 kinase domain and C-terminal insertion domain, inducing an opening of the head domain that provides access to the active site. SMG-8 and SMG-9 interact with the SMG-1 C-insertion and promote high-affinity UPF1 binding to SMG-1-8-9, as well as decelerated SMG-1 kinase activity and enhanced stringency of phosphorylation site selection. The presence of UPF2 destabilizes the SMG-1-8-9-UPF1 complex leading to substrate release. Our results suggest an intricate molecular network of SMG-8, SMG-9 and the SMG-1 C-insertion domain that governs UPF1 substrate recruitment and phosphorylation by SMG-1 kinase, an event that is central to trigger mRNA decay. |
リンク | Nucleic Acids Res / PubMed:26130714 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 17.0 - 19.0 Å |
構造データ | EMDB-3065: EMDB-3066: |
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