6gx9 | pdb_00006gx9

Crystal structure of the TNPO3 - CPSF6 RSLD complex

spinqualitylabelsall models 6gx9, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6gx9 is a 4 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 2.7Å Ligands: BCN, BEN, MG, SEP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease TNPO3_HUMAN Primary biliary cirrhosis;Autosomal dominant limb-girdle muscular dystrophy type 1F. Function TNPO3_HUMAN Seems to function in nuclear protein import as nuclear transport receptor. In vitro, mediates the nuclear import of splicing factor SR proteins RBM4, SFRS1 and SFRS2, by recognizing phosphorylated RS domains. Publication Abstract from PubMed Cleavage factor I mammalian (CFIm) complex, composed of cleavage and polyadenylation specificity factor 5 (CPSF5) and serine/arginine-like protein CPSF6, regulates alternative polyadenylation (APA). Loss of CFIm function results in proximal polyadenylation site usage, shortening mRNA 3' untranslated regions (UTRs). Although CPSF6 plays additional roles in human disease, its nuclear translocation mechanism remains unresolved. Two beta-karyopherins, transportin (TNPO) 1 and TNPO3, can bind CPSF6 in vitro, and we demonstrate here that while the TNPO1 binding site is dispensable for CPSF6 nuclear import, the arginine/serine (RS)-like domain (RSLD) that mediates TNPO3 binding is critical. The crystal structure of the RSLD-TNPO3 complex revealed potential CPSF6 interaction residues, which were confirmed to mediate TNPO3 binding and CPSF6 nuclear import. Both binding and nuclear import were independent of RSLD phosphorylation, though a hyperphosphorylated mimetic mutant failed to bind TNPO3 and mislocalized to the cell cytoplasm. Although hypophosphorylated CPSF6 largely supported normal polyadenylation site usage, a significant number of mRNAs harbored unnaturally extended 3' UTRs, similar to what is observed when other APA regulators, such as CFIIm component proteins, are depleted. Our results clarify the mechanism of CPSF6 nuclear import and highlight differential roles for RSLD phosphorylation in nuclear translocation versus regulation of APA. Differential role for phosphorylation in alternative polyadenylation function versus nuclear import of SR-like protein CPSF6.,Jang S, Cook NJ, Pye VE, Bedwell GJ, Dudek AM, Singh PK, Cherepanov P, Engelman AN Nucleic Acids Res. 2019 Mar 27. pii: 5420532. doi: 10.1093/nar/gkz206. PMID:30916345 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Importin 3D structures

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