3fmo

Crystal structure of the nucleoporin Nup214 in complex with the DEAD-box helicase Ddx19

spinqualitylabelsall models 3fmo, resolution 2.51Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3fmo is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ADP, GOL Related: 3fmp Gene: NUP214, CAIN, CAN, KIAA0023 (HUMAN), DDX19B, DBP5, DDX19 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [NU214_HUMAN] Note=A chromosomal aberration involving NUP214 is found in a subset of acute myeloid leukemia (AML); also known as acute non-lymphocytic leukemia. Translocation t(6;9)(p23;q34) with DEK. It results in the formation of a DEK-CAN fusion gene. Note=A chromosomal aberration involving NUP214 is found in some cases of acute undifferentiated leukemia (AUL). Translocation t(6;9)(q21;q34.1) with SET. Function [NU214_HUMAN] May serve as a docking site in the receptor-mediated import of substrates across the nuclear pore complex. [DD19B_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. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Key steps in the export of mRNA from the nucleus to the cytoplasm are the transport through the nuclear pore complex (NPC) and the subsequent remodeling of messenger RNA-protein (mRNP) complexes that occurs at the cytoplasmic side of the NPC. Crucial for these events is the recruitment of the DEAD-box helicase Ddx19 to the cytoplasmic filaments of the NPC that is mediated by the nucleoporin Nup214. Here, we present the crystal structure of the Nup214 N-terminal domain in complex with Ddx19 in its ADP-bound state at 2.5 A resolution. Strikingly, the interaction surfaces are not only evolutionarily conserved but also exhibit strongly opposing surface potentials, with the helicase surface being positively and the Nup214 surface being negatively charged. We speculate that the positively charged surface of the interacting ADP-helicase binds competitively to a segment of mRNA of a linearized mRNP, passing through the NPC on its way to the cytoplasm. As a result, the ADP-helicase would dissociate from Nup214 and replace a single bound protein from the mRNA. One cycle of protein replacement would be accompanied, cooperatively, by nucleotide exchange, ATP hydrolysis, release of the ADP-helicase from mRNA and its rebinding to Nup214. Repeat of these cycles would remove proteins from a mRNP, one at a time, akin to a ratchet mechanism for mRNA export. Structural and functional analysis of the interaction between the nucleoporin Nup214 and the DEAD-box helicase Ddx19.,Napetschnig J, Kassube SA, Debler EW, Wong RW, Blobel G, Hoelz A Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3089-94. Epub 2009 Feb 10. PMID:19208808 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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