6B4K

Crystal structure of human DDX19B(AMPPNP)

Summary for 6B4K

• Entry DOI: 10.2210/pdb6b4k/pdb
• Descriptor: ATP-dependent RNA helicase DDX19B, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (5 entities in total)
• Functional Keywords: complex, nuclear pore complex, mrna export, dead-box helicase, transport protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 98683.14

Authors

Lin, D.H.,Correia, A.R.,Cai, S.W.,Huber, F.M.,Jette, C.A.,Hoelz, A. (deposition date: 2017-09-26, release date: 2018-06-20, Last modification date: 2023-10-04)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.2 Å)