2OPU

Solution NMR Structure of the First Domain of KSRP

2OPU の概要

• エントリーDOI: 10.2210/pdb2opu/pdb
• 関連するPDBエントリー: 2HH2 2HH3
• 分子名称: KHSRP protein (1 entity in total)
• 機能のキーワード: kh domain, rna binding protein, ksrp
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9411.70

構造登録者

Diaz-Moreno, I.,Ramos, A.,Garcia-Mayoral, M.F.,Hollingworth, D. (登録日: 2007-01-30, 公開日: 2008-02-26, 最終更新日: 2023-12-27)

主引用文献

Diaz-Moreno, I.,Hollingworth, D.,Frenkiel, T.A.,Kelly, G.,Martin, S.,Howell, S.,Garcia-Mayoral, M.,Gherzi, R.,Briata, P.,Ramos, A.
Phosphorylation-mediated unfolding of a KH domain regulates KSRP localization via 14-3-3 binding.
Nat.Struct.Mol.Biol., 16:238-246, 2009

PubMed Abstract: The AU-rich element (ARE)-mediated mRNA-degradation activity of the RNA binding K-homology splicing regulator protein (KSRP) is regulated by phosphorylation of a serine within its N-terminal KH domain (KH1). In the cell, phosphorylation promotes the interaction of KSRP and 14-3-3zeta protein and impairs the ability of KSRP to promote the degradation of its RNA targets. Here we examine the molecular details of this mechanism. We report that phosphorylation leads to the unfolding of the structurally atypical and unstable KH1, creating a site for 14-3-3zeta binding. Using this site, 14-3-3zeta discriminates between phosphorylated and unphosphorylated KH1, driving the nuclear localization of KSRP. 14-3-3zeta -KH1 interaction regulates the mRNA-decay activity of KSRP by sequestering the protein in a separate functional pool. This study demonstrates how an mRNA-degradation pathway is connected to extracellular signaling networks through the reversible unfolding of a protein domain.

PubMed: 19198587
DOI: 10.1038/nsmb.1558

実験手法

SOLUTION NMR