6Z3R

Structure of SMG1-8-9 kinase complex bound to UPF1-LSQ

6Z3R の概要

• エントリーDOI: 10.2210/pdb6z3r/pdb
• EMDBエントリー: 11063
• 分子名称: 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)
• 機能のキーワード: cryo-em, structural biology, nonsense-mediated mrna decay, rna quality control, pikk, nmd, substrate, phosphorylation, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 550062.01

構造登録者

Langer, L.M.,Gat, Y.,Conti, E. (登録日: 2020-05-21, 公開日: 2020-06-24, 最終更新日: 2024-05-22)

主引用文献

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

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: 32469312
DOI: 10.7554/eLife.57127

実験手法

ELECTRON MICROSCOPY (2.97 Å)