9ZEB

Cryo-EM structure of the TREX-2.1 complex (Thp3/Csn12/Sem1) bound to the DEAD-box ATPase Sub2

This is a non-PDB format compatible entry.

Summary for 9ZEB

• Entry DOI: 10.2210/pdb9zeb/pdb
• EMDB information: 74098
• Descriptor: Protein THP3, Cop9 signalosome complex subunit 12, 26S proteasome complex subunit SEM1, ... (5 entities in total)
• Functional Keywords: trex-2, trex-2 like, sub2, mrna nuclear export, rna binding protein
• Biological source: Saccharomyces cerevisiae (brewer's yeast); More
• Total number of polymer chains: 4
• Total formula weight: 151508.15

Authors

Angelos, A.E.,Clarke, B.P.,Xie, Y.,Ren, Y. (deposition date: 2025-11-28, release date: 2026-09-30)

Primary citation

Angelos, A.E.,Asada, R.,Clarke, B.P.,Hill, P.S.,Li, L.,Mei, M.,Smith, J.L.,Xie, E.R.,Reter, W.C.,Smithee, S.J.,Xie, Y.,Montpetit, B.,Ren, Y.
Conserved mRNP remodeling mechanism of the TREX-2.1 complex.
Nucleic Acids Res., 54:-, 2026

PubMed Abstract: Processing, packaging, and nuclear export of messenger ribonucleoprotein particles (mRNPs) are critical for eukaryotic gene expression, with the DEAD-box ATPase DDX39B (yeast Sub2) playing a central role in mRNP processing and remodeling. Our recent studies identified human TREX-2 (GANP•PCID2•DSS1), yeast TREX-2 (Sac3•Thp1•Sem1), and a related human TREX-2.1 complex (LENG8•PCID2•DSS1) as key regulators of DDX39B/Sub2. Here, we characterize the yeast TREX-2.1 (scTREX-2.1) complex, composed of Thp3, Csn12, and Sem1. We show that the scTREX-2.1 complex directly interacts with Sub2 and co-occupies a fraction of CBC-containing mRNPs with Sub2. Using cryo-electron microscopy , we determined the structure of scTREX-2.1 bound to Sub2, revealing a conserved "trigger loop" mechanism by which scTREX-2.1 regulates Sub2 activity. Functional assays show that disruption of scTREX-2.1 leads to the accumulation of intron-containing pre-mRNAs. These findings uncover a conserved mechanism from yeast to humans by which TREX-2 and TREX-2.1 complexes regulate Sub2/DDX39B during nuclear mRNP maturation, providing insights into the coordination of mRNP remodeling and processing prior to nuclear export.

PubMed: 42728799
DOI: 10.1093/nar/gkag884

Experimental method

ELECTRON MICROSCOPY (3.72 Å)