8RD3

Crystal structure of Saccharomyces cerevisiae Nmd4 protein bound to Upf1 helicase domain

8RD3 の概要

• エントリーDOI: 10.2210/pdb8rd3/pdb
• 分子名称: ATP-dependent helicase NAM7, Nonsense-mediated decay protein 4, 1,2-ETHANEDIOL, ... (7 entities in total)
• 機能のキーワード: nonsense-mediated mrna decay, pin domain, helicase, protein complex, rna binding protein
• 由来する生物種: Saccharomyces cerevisiae S288C; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 98689.93

構造登録者

Barbarin-Bocahu, I.,Graille, M. (登録日: 2023-12-07, 公開日: 2024-08-14, 最終更新日: 2025-02-26)

主引用文献

Barbarin-Bocahu, I.,Ulryck, N.,Rigobert, A.,Ruiz Gutierrez, N.,Decourty, L.,Raji, M.,Garkhal, B.,Le Hir, H.,Saveanu, C.,Graille, M.
Structure of the Nmd4-Upf1 complex supports conservation of the nonsense-mediated mRNA decay pathway between yeast and humans.
Plos Biol., 22:e3002821-e3002821, 2024

PubMed Abstract: The nonsense-mediated mRNA decay (NMD) pathway clears eukaryotic cells of mRNAs containing premature termination codons (PTCs) or normal stop codons located in specific contexts. It therefore plays an important role in gene expression regulation. The precise molecular mechanism of the NMD pathway has long been considered to differ substantially from yeast to metazoa, despite the involvement of universally conserved factors such as the central ATP-dependent RNA-helicase Upf1. Here, we describe the crystal structure of the yeast Upf1 bound to its recently identified but yet uncharacterized partner Nmd4, show that Nmd4 stimulates Upf1 ATPase activity and that this interaction contributes to the elimination of NMD substrates. We also demonstrate that a region of Nmd4 critical for the interaction with Upf1 in yeast is conserved in the metazoan SMG6 protein, another major NMD factor. We show that this conserved region is involved in the interaction of SMG6 with UPF1 and that mutations in this region affect the levels of endogenous human NMD substrates. Our results support the universal conservation of the NMD mechanism in eukaryotes.

PubMed: 39331656
DOI: 10.1371/journal.pbio.3002821

実験手法

X-RAY DIFFRACTION (2.402 Å)