6B4I

Crystal structure of human Gle1 CTD-Nup42 GBM-DDX19B(ADP) complex

6B4I の概要

• エントリーDOI: 10.2210/pdb6b4i/pdb
• 分子名称: Nucleoporin GLE1, Nucleoporin like 2, ATP-dependent RNA helicase DDX19B, ... (5 entities in total)
• 機能のキーワード: complex, nuclear pore complex, mrna export, dead-box helicase, transport protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 182543.35

構造登録者

Lin, D.H.,Correia, A.R.,Cai, S.W.,Huber, F.M.,Jette, C.A.,Hoelz, A. (登録日: 2017-09-26, 公開日: 2018-06-20, 最終更新日: 2024-03-13)

主引用文献

Lin, D.H.,Correia, A.R.,Cai, S.W.,Huber, F.M.,Jette, C.A.,Hoelz, A.
Structural and functional analysis of mRNA export regulation by the nuclear pore complex.
Nat Commun, 9:2319-2319, 2018

PubMed Abstract: The nuclear pore complex (NPC) controls the passage of macromolecules between the nucleus and cytoplasm, but how the NPC directly participates in macromolecular transport remains poorly understood. In the final step of mRNA export, the DEAD-box helicase DDX19 is activated by the nucleoporins Gle1, Nup214, and Nup42 to remove Nxf1•Nxt1 from mRNAs. Here, we report crystal structures of Gle1•Nup42 from three organisms that reveal an evolutionarily conserved binding mode. Biochemical reconstitution of the DDX19 ATPase cycle establishes that human DDX19 activation does not require IP, unlike its fungal homologs, and that Gle1 stability affects DDX19 activation. Mutations linked to motor neuron diseases cause decreased Gle1 thermostability, implicating nucleoporin misfolding as a disease determinant. Crystal structures of human Gle1•Nup42•DDX19 reveal the structural rearrangements in DDX19 from an auto-inhibited to an RNA-binding competent state. Together, our results provide the foundation for further mechanistic analyses of mRNA export in humans.

PubMed: 29899397
DOI: 10.1038/s41467-018-04459-3

実験手法

X-RAY DIFFRACTION (3.619 Å)