9D43

Cryo-EM structure of unliganded yeast Exportin Msn5

9D43 の概要

• エントリーDOI: 10.2210/pdb9d43/pdb
• EMDBエントリー: 46548
• 分子名称: Protein MSN5 (1 entity in total)
• 機能のキーワード: karyopherin, exportin, nuclear export, transport protein
• 由来する生物種: Saccharomyces cerevisiae (brewer's yeast)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 143067.19

構造登録者

Fung, H.Y.J.,Chook, Y.M. (登録日: 2024-08-12, 公開日: 2025-03-19, 最終更新日: 2025-04-02)

主引用文献

Fung, H.Y.J.,Mittal, S.R.,Niesman, A.B.,Jiou, J.,Shakya, B.,Yoshizawa, T.,Cansizoglu, A.E.,Rout, M.P.,Chook, Y.M.
Phosphate-dependent nuclear export via a non-classical NES class recognized by exportin Msn5.
Nat Commun, 16:2580-2580, 2025

PubMed Abstract: Gene expression in response to environmental stimuli is dependent on nuclear localization of key signaling components, which can be tightly regulated by phosphorylation. This is exemplified by the phosphate-sensing transcription factor Pho4, which requires phosphorylation for nuclear export by the yeast exportin Msn5. Here, we present a high resolution cryogenic-electron microscopy structure showing the phosphorylated 35-residue nuclear export signal of Pho4, which binds the concave surface of Msn5 through two Pho4 phospho-serines that align with two Msn5 basic patches. These findings characterize a mechanism of phosphate-specific recognition mediated by a non-classical signal distinct from that for Exportin-1. Furthermore, the discovery that unliganded Msn5 is autoinhibited explains the positive cooperativity of Pho4/Ran-binding and proposes a mechanism for Pho4's release in the cytoplasm. These findings advance our understanding of the diversity of signals that drive nuclear export and how cargo phosphorylation is crucial in regulating nuclear transport and controlling cellular signaling pathways.

PubMed: 40089503
DOI: 10.1038/s41467-025-57752-3

実験手法

ELECTRON MICROSCOPY (3.39 Å)