6Z3R
Structure of SMG1-8-9 kinase complex bound to UPF1-LSQ
Summary for 6Z3R
| Entry DOI | 10.2210/pdb6z3r/pdb |
| EMDB information | 11063 |
| Descriptor | Serine/threonine-protein kinase SMG1,Serine/threonine-protein kinase SMG1,SMG1,Serine/threonine-protein kinase SMG1,Serine/threonine-protein kinase SMG1,Serine/threonine-protein kinase SMG1, Protein SMG8, Protein SMG9, ... (8 entities in total) |
| Functional Keywords | cryo-em, structural biology, nonsense-mediated mrna decay, rna quality control, pikk, nmd, substrate, phosphorylation, transferase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 550062.01 |
| Authors | Langer, L.M.,Gat, Y.,Conti, E. (deposition date: 2020-05-21, release date: 2020-06-24, Last modification date: 2024-05-22) |
| Primary citation | Langer, L.M.,Gat, Y.,Bonneau, F.,Conti, E. Structure of substrate-bound SMG1-8-9 kinase complex reveals molecular basis for phosphorylation specificity. Elife, 9:-, 2020 Cited by PubMed Abstract: PI3K-related kinases (PIKKs) are large Serine/Threonine (Ser/Thr)-protein kinases central to the regulation of many fundamental cellular processes. PIKK family member SMG1 orchestrates progression of an RNA quality control pathway, termed nonsense-mediated mRNA decay (NMD), by phosphorylating the NMD factor UPF1. Phosphorylation of UPF1 occurs in its unstructured N- and C-terminal regions at Serine/Threonine-Glutamine (SQ) motifs. How SMG1 and other PIKKs specifically recognize SQ motifs has remained unclear. Here, we present a cryo-electron microscopy (cryo-EM) reconstruction of a human SMG1-8-9 kinase complex bound to a UPF1 phosphorylation site at an overall resolution of 2.9 Å. This structure provides the first snapshot of a human PIKK with a substrate-bound active site. Together with biochemical assays, it rationalizes how SMG1 and perhaps other PIKKs specifically phosphorylate Ser/Thr-containing motifs with a glutamine residue at position +1 and a hydrophobic residue at position -1, thus elucidating the molecular basis for phosphorylation site recognition. PubMed: 32469312DOI: 10.7554/eLife.57127 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.97 Å) |
Structure validation
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