5w0n | pdb_00005w0n

Structure of human TUT7 catalytic module (CM) in complex with UMPNPP and U2 RNA

spinqualitylabelsall models 5w0n, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5w0n is a 3 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 2.497Å Ligands: 2KH, IOD, MG, SO4, UPU, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function TUT7_HUMAN Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:19703396, PubMed:25480299). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets (PubMed:25480299). Also acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of some miRNA precursors, including that of let-7 (pre-let-7). Uridylated pre-let-7 RNA is not processed by Dicer and undergo degradation. Pre-let-7 uridylation is strongly enhanced in the presence of LIN28A (PubMed:22898984). Due to functional redundancy between ZCCHC6 and ZCCHC11, the identification of the specific role of each of these proteins is difficult. Publication Abstract from PubMed The uridyl transferases TUT4 and TUT7 (collectively called TUT4(7)) switch between two modes of activity, either promoting expression of let-7 microRNA (monoU) or marking it for degradation (oligoU). Lin28 modulates the switch via recruitment of TUT4(7) to the precursor pre-let-7 in stem cells and human cancers. We found that TUT4(7) utilize two multidomain functional modules during the switch from monoU to oligoU. The catalytic module (CM) is essential for both activities, while the Lin28-interacting module (LIM) is indispensable for oligoU. A TUT7 CM structure trapped in the monoU activity staterevealed a duplex-RNA-binding pocket that orients group II pre-let-7 hairpins to favor monoU addition. Conversely, the switch to oligoU requires the ZK domain of Lin28 to drive the formation of a stable ternary complex between pre-let-7 and the inactive LIM. Finally, ZK2 of TUT4(7) aids oligoU addition by engaging the growing oligoU tail through uracil-specific interactions. Multi-domain utilization by TUT4 and TUT7 in control of let-7 biogenesis.,Faehnle CR, Walleshauser J, Joshua-Tor L Nat Struct Mol Biol. 2017 Aug;24(8):658-665. doi: 10.1038/nsmb.3428. Epub 2017, Jul 3. PMID:28671666 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also RNA uridylyltransferase

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