6syt
From Proteopedia
Structure of the SMG1-SMG8-SMG9 complex
Structural highlights
Disease[SMG9_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. Function[SMG9_HUMAN] Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons (PubMed:19417104). Is recruited by release factors to stalled ribosomes together with SMG1 and SMG8 (forming the SMG1C protein kinase complex) and, in the SMG1C complex, is required for the efficient association between SMG1 and SMG8 (PubMed:19417104). Plays a role in brain, heart, and eye development (By similarity).[UniProtKB:Q9DB90][1] [SMG8_HUMAN] Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Is recruited by release factors to stalled ribosomes together with SMG1 and SMG9 (forming the SMG1C protein kinase complex) and, in the SMG1C complex, is required to mediate the recruitment of SMG1 to the ribosome:SURF complex and to suppress SMG1 kinase activity until the ribosome:SURF complex locates the exon junction complex (EJC). Acts as a regulator of kinase activity.[2] Publication Abstract from PubMedWe report the 3.45-A resolution cryo-EM structure of human SMG1-SMG8-SMG9, a phosphatidylinositol-3-kinase (PI(3)K)-related protein kinase (PIKK) complex central to messenger RNA surveillance. Structural and MS analyses reveal the presence of inositol hexaphosphate (InsP6) in the SMG1 kinase. We show that the InsP6-binding site is conserved in mammalian target of rapamycin (mTOR) and potentially other PIKK members, and that it is required for optimal in vitro phosphorylation of both SMG1 and mTOR substrates. InsP6 binding to PIKK kinases revealed by the cryo-EM structure of an SMG1-SMG8-SMG9 complex.,Gat Y, Schuller JM, Lingaraju M, Weyher E, Bonneau F, Strauss M, Murray PJ, Conti E Nat Struct Mol Biol. 2019 Dec;26(12):1089-1093. doi: 10.1038/s41594-019-0342-7., Epub 2019 Dec 2. PMID:31792449[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Large Structures | Conti, E | Gat, Y | Schuller, J M | G-fold protein | Ip6 | Kinase | Nmd | Pikk family | Signaling protein