9DLR

Cryo-EM structure of the human TREX-2.1 complex (LENG8/PCID2/DSS1) bound to the N-terminal motif of DDX39B(UAP56)

9DLR の概要

• エントリーDOI: 10.2210/pdb9dlr/pdb
• EMDBエントリー: 46983
• 分子名称: Leukocyte receptor cluster member 8, PCI domain-containing protein 2, 26S proteasome complex subunit SEM1, ... (4 entities in total)
• 機能のキーワード: mrna nuclear export, trex, trex-2, leng8, uap56, ddx39b, rna binding protein, rna binding protein-hydrolase complex, rna binding protein/hydrolase
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 139346.05

構造登録者

Clarke, B.P.,Xie, Y.,Ren, Y. (登録日: 2024-09-11, 公開日: 2025-09-17, 最終更新日: 2025-11-12)

主引用文献

Clarke, B.P.,Gao, S.,Mei, M.,Xie, D.,Angelos, A.E.,Vazhavilla, A.,Hill, P.S.,Cagatay, T.,Batten, K.,Shay, J.W.,Xie, Y.,Fontoura, B.M.A.,Ren, Y.
Structural mechanism of DDX39B regulation by human TREX-2 and a related complex in mRNP remodeling.
Nat Commun, 16:5471-5471, 2025

PubMed Abstract: Nuclear export of mRNAs in the form of messenger ribonucleoprotein particles (mRNPs) is an obligatory step for eukaryotic gene expression. The DEAD-box ATPase DDX39B (also known as UAP56) is a multifunctional regulator of nuclear mRNPs. How DDX39B mediates mRNP assembly and export in a controlled manner remains elusive. Here, we identify a novel complex TREX-2.1 localized in the nucleus that facilitates the release of DDX39B from the mRNP. TREX-2.1 is composed of three subunits, LENG8, PCID2, and DSS1, and shares the latter two subunits with the nuclear pore complex-associated TREX-2 complex. Cryo-EM structures of TREX-2.1/DDX39B and TREX-2/DDX39B identify a conserved trigger loop in the LENG8 and GANP subunit of the respective TREX-2.1 and TREX-2 complex that is critical for DDX39B regulation. RNA sequencing from LENG8 knockdown cells shows that LENG8 influences the nucleocytoplasmic ratio of a subset of mRNAs with high GC content. Together, our findings lead to a mechanistic understanding of the functional cycle of DDX39B and its regulation by TREX-2 and TREX-2.1 in mRNP processing.

PubMed: 40595470
DOI: 10.1038/s41467-025-60547-1

実験手法

ELECTRON MICROSCOPY (3.08 Å)