4ALP
The Lin28b Cold shock domain in complex with hexauridine
Summary for 4ALP
| Entry DOI | 10.2210/pdb4alp/pdb |
| Related | 4A75 4A76 |
| Descriptor | LIN28 ISOFORM B, HEXA URIDINE, GLYCEROL, ... (4 entities in total) |
| Functional Keywords | chaperone-rna complex, transcription, lin-28, rna, let-7, mirna, chaperone/rna |
| Biological source | XENOPUS TROPICALIS More |
| Total number of polymer chains | 5 |
| Total formula weight | 41745.15 |
| Authors | Mayr, F.,Schuetz, A.,Doege, N.,Heinemann, U. (deposition date: 2012-03-05, release date: 2012-09-05, Last modification date: 2024-05-08) |
| Primary citation | Mayr, F.,Schutz, A.,Doge, N.,Heinemann, U. The Lin28 Cold-Shock Domain Remodels Pre-Let-7 Microrna. Nucleic Acids Res., 40:7492-, 2012 Cited by PubMed Abstract: The RNA-binding protein Lin28 regulates the processing of a developmentally important group of microRNAs, the let-7 family. Lin28 blocks the biogenesis of let-7 in embryonic stem cells and thereby prevents differentiation. It was shown that both RNA-binding domains (RBDs) of this protein, the cold-shock domain (CSD) and the zinc-knuckle domain (ZKD) are indispensable for pri- or pre-let-7 binding and blocking its maturation. Here, we systematically examined the nucleic acid-binding preferences of the Lin28 RBDs and determined the crystal structure of the Lin28 CSD in the absence and presence of nucleic acids. Both RNA-binding domains bind to single-stranded nucleic acids with the ZKD mediating specific binding to a conserved GGAG motif and the CSD showing only limited sequence specificity. However, only the isolated Lin28 CSD, but not the ZKD, can bind with a reasonable affinity to pre-let-7 and thus is able to remodel the terminal loop of pre-let-7 including the Dicer cleavage site. Further mutagenesis studies reveal that the Lin28 CSD induces a conformational change in the terminal loop of pre-let-7 and thereby facilitates a subsequent specific binding of the Lin28 ZKD to the conserved GGAG motif. PubMed: 22570413DOI: 10.1093/NAR/GKS355 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.48 Å) |
Structure validation
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