5UDZ

Human LIN28A in complex with let-7f-1 microRNA pre-element

Summary for 5UDZ

• Entry DOI: 10.2210/pdb5udz/pdb
• Descriptor: Protein lin-28 homolog A, let-7f-1 pre-element, ZINC ION, ... (4 entities in total)
• Functional Keywords: microrna, let-7, lin28, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 48454.36

Authors

Nam, Y.,Wang, L.,Sliz, P. (deposition date: 2016-12-29, release date: 2017-03-22, Last modification date: 2023-10-04)

Primary citation

Wang, L.,Nam, Y.,Lee, A.K.,Yu, C.,Roth, K.,Chen, C.,Ransey, E.M.,Sliz, P.
LIN28 Zinc Knuckle Domain Is Required and Sufficient to Induce let-7 Oligouridylation.
Cell Rep, 18:2664-2675, 2017

PubMed Abstract: LIN28 is an RNA binding protein that plays crucial roles in pluripotency, glucose metabolism, tissue regeneration, and tumorigenesis. LIN28 binds to the let-7 primary and precursor microRNAs through bipartite recognition and induces degradation of let-7 precursors (pre-let-7) by promoting oligouridylation by terminal uridylyltransferases (TUTases). Here, we report that the zinc knuckle domain (ZKD) of mouse LIN28 recruits TUT4 to initiate the oligouridylation of let-7 precursors. Our crystal structure of human LIN28 in complex with a fragment of pre-let-7f-1 determined to 2.0 Å resolution shows that the interaction between ZKD and RNA is constrained to a small cavity with a high druggability score. We demonstrate that the specific interaction between ZKD and pre-let-7 is necessary and sufficient to induce oligouridylation by recruiting the N-terminal fragment of TUT4 (NTUT4) and the formation of a stable ZKD:NTUT4:pre-let-7 ternary complex is crucial for the acquired processivity of TUT4.

PubMed: 28297670
DOI: 10.1016/j.celrep.2017.02.044

Experimental method

X-RAY DIFFRACTION (2 Å)