5W0N

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

Summary for 5W0N

• Entry DOI: 10.2210/pdb5w0n/pdb
• Descriptor: Terminal uridylyltransferase 7, MAGNESIUM ION, 5'-O-[(S)-hydroxy{[(S)-hydroxy(phosphonooxy)phosphoryl]amino}phosphoryl]uridine, ... (8 entities in total)
• Functional Keywords: terminal uridyltransferase, tutase, transferase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : Q5VYS8
• Total number of polymer chains: 3
• Total formula weight: 143758.46

Authors

Faehnle, C.R.,Walleshauser, J.,Joshua-Tor, L. (deposition date: 2017-05-31, release date: 2017-06-28, Last modification date: 2023-10-04)

Primary citation

Faehnle, C.R.,Walleshauser, J.,Joshua-Tor, L.
Multi-domain utilization by TUT4 and TUT7 in control of let-7 biogenesis.
Nat. Struct. Mol. Biol., 24:658-665, 2017

PubMed Abstract: 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.

PubMed: 28671666
DOI: 10.1038/nsmb.3428

Experimental method

X-RAY DIFFRACTION (2.497 Å)