9DZ6

Cryo-EM structure of yeast Exportin Msn5 bound to RanGTP and Pho4 (not modeled) (State 3-1)

Summary for 9DZ6

• Entry DOI: 10.2210/pdb9dz6/pdb
• Related: 9D45 9DXM
• EMDB information: 47325
• Descriptor: Protein MSN5, GTP-binding nuclear protein GSP1/CNR1, GUANOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: karyopherin, exportin, nuclear export, transport protein
• Biological source: Saccharomyces cerevisiae (brewer's yeast); More
• Total number of polymer chains: 2
• Total formula weight: 164898.19

Authors

Fung, H.Y.J.,Chook, Y.M. (deposition date: 2024-10-15, release date: 2025-03-19, Last modification date: 2025-04-02)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.1 Å)