6b4k
Crystal structure of human DDX19B(AMPPNP)Crystal structure of human DDX19B(AMPPNP)
Structural highlights
FunctionDD19B_HUMAN ATP-dependent RNA helicase involved in mRNA export from the nucleus. Rather than unwinding RNA duplexes, DDX19B functions as a remodeler of ribonucleoprotein particles, whereby proteins bound to nuclear mRNA are dissociated and replaced by cytoplasmic mRNA binding proteins. 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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