2LI8

The solution structure of the Lin28-ZnF domains bound to AGGAGAU of pre-let-7 miRNA

Summary for 2LI8

• Entry DOI: 10.2210/pdb2li8/pdb
• Related: 2CQF
• NMR Information: BMRB: 17883
• Descriptor: Protein lin-28 homolog A, RNA (5'-R(*AP*GP*GP*AP*GP*AP*U)-3'), ZINC ION (3 entities in total)
• Functional Keywords: zinc finger, micro rna, transcription-rna complex, transcription/rna
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q9H9Z2
• Total number of polymer chains: 2
• Total formula weight: 10448.64

Authors

Allain, F.H.-T.,Loughlin, F.E. (deposition date: 2011-08-25, release date: 2011-12-07, Last modification date: 2024-05-01)

Primary citation

Loughlin, F.E.,Gebert, L.F.,Towbin, H.,Brunschweiger, A.,Hall, J.,Allain, F.H.
Structural basis of pre-let-7 miRNA recognition by the zinc knuckles of pluripotency factor Lin28.
Nat.Struct.Mol.Biol., 19:84-89, 2011

PubMed Abstract: Lin28 inhibits the biogenesis of let-7 miRNAs through a direct interaction with the terminal loop of pre-let-7. This interaction requires the zinc-knuckle domains of Lin28. We show that the zinc knuckle domains of Lin28 are sufficient to provide binding selectivity for pre-let-7 miRNAs and present the NMR structure of human Lin28 zinc knuckles bound to the short sequence 5'-AGGAGAU-3'. The structure reveals that each zinc knuckle recognizes an AG dinucleotide separated by a single nucleotide spacer. This defines a new 5'-NGNNG-3' consensus motif that explains how Lin28 selectively recognizes pre-let-7 family members. Binding assays in cell lysates and functional assays in cultured cells demonstrate that the interactions observed in the solution structure also occur between the full-length protein and members of the pre-let-7 family. The consensus sequence explains several seemingly disparate previously published observations on the binding properties of Lin28.

PubMed: 22157959
DOI: 10.1038/nsmb.2202

Experimental method

SOLUTION NMR