6b4h
Crystal structure of Chaetomium thermophilum Gle1 CTD-Nup42 GBM-IP6 complexCrystal structure of Chaetomium thermophilum Gle1 CTD-Nup42 GBM-IP6 complex
Structural highlights
Function[AMO1_CHATD] Functions as a component of the nuclear pore complex (NPC). NPC components, collectively referred to as nucleoporins (NUPs), can play the role of both NPC structural components and of docking or interaction partners for transiently associated nuclear transport factors. Active directional transport is assured by both, a Phe-Gly (FG) repeat affinity gradient for these transport factors across the NPC and a transport cofactor concentration gradient across the nuclear envelope (GSP1 and GSP2 GTPases associated predominantly with GTP in the nucleus, with GDP in the cytoplasm). AMO1 is specifically important for nuclear protein and mRNA export.[UniProtKB:P49686] [GLE1_CHATD] Functions as a component of the nuclear pore complex (NPC). NPC components, collectively referred to as nucleoporins (NUPs), can play the role of both NPC structural components and of docking or interaction partners for transiently associated nuclear transport factors.[UniProtKB:Q12315] Publication Abstract from PubMedThe 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 IP6, 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. Structural and functional analysis of mRNA export regulation by the nuclear pore complex.,Lin DH, Correia AR, Cai SW, Huber FM, Jette CA, Hoelz A Nat Commun. 2018 Jun 13;9(1):2319. doi: 10.1038/s41467-018-04459-3. PMID:29899397[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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