6ieh

Crystal structures of the hMTR4-NRDE2 complexCrystal structures of the hMTR4-NRDE2 complex

Structural highlights 6ieh is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.892Å Ligands: , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MTREX_HUMAN Component of exosome targeting complexes. Subunit of the trimeric nuclear exosome targeting (NEXT) complex, a complex that directs a subset of non-coding short-lived RNAs for exosomal degradation. Subunit of the trimeric poly(A) tail exosome targeting (PAXT) complex, a complex that directs a subset of long and polyadenylated poly(A) RNAs for exosomal degradation. The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its cofactor MTREX, which links to RNA-binding protein adapters (PubMed:27871484). May be involved in pre-mRNA splicing. Associated with the RNA exosome complex and involved in the 3'-processing of the 7S pre-RNA to the mature 5.8S rRNA. Publication Abstract from PubMed The exosome functions in the degradation of diverse RNA species, yet how it is negatively regulated remains largely unknown. Here, we show that NRDE2 forms a 1:1 complex with MTR4, a nuclear exosome cofactor critical for exosome recruitment, via a conserved MTR4-interacting domain (MID). Unexpectedly, NRDE2 mainly localizes in nuclear speckles, where it inhibits MTR4 recruitment and RNA degradation, and thereby ensures efficient mRNA nuclear export. Structural and biochemical data revealed that NRDE2 interacts with MTR4's key residues, locks MTR4 in a closed conformation, and inhibits MTR4 interaction with the exosome as well as proteins important for MTR4 recruitment, such as the cap-binding complex (CBC) and ZFC3H1. Functionally, MID deletion results in the loss of self-renewal of mouse embryonic stem cells. Together, our data pinpoint NRDE2 as a nuclear exosome negative regulator that ensures mRNA stability and nuclear export. NRDE2 negatively regulates exosome functions by inhibiting MTR4 recruitment and exosome interaction.,Wang J, Chen J, Wu G, Zhang H, Du X, Chen S, Zhang L, Wang K, Fan J, Gao S, Wu X, Zhang S, Kuai B, Zhao P, Chi B, Wang L, Li G, Wong CCL, Zhou Y, Li J, Yun C, Cheng H Genes Dev. 2019 Mar 6. pii: gad.322602.118. doi: 10.1101/gad.322602.118. PMID:30842217 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Exosome 3D structures Helicase 3D structures

spinqualitylabelsall models 6ieh, resolution 2.89Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image