4A4I

Crystal structure of the human Lin28b cold shock domain

Summary for 4A4I

• Entry DOI: 10.2210/pdb4a4i/pdb
• Related: 4A65 4A76 4ALP
• Descriptor: PROTEIN LIN-28 HOMOLOG B, GLYCEROL, SULFATE ION, ... (4 entities in total)
• Functional Keywords: rna binding protein
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm: Q6ZN17
• Total number of polymer chains: 2
• Total formula weight: 19948.73

Authors

Mayr, F.,Schuetz, A.,Doege, N.,Heinemann, U. (deposition date: 2011-10-14, release date: 2012-08-08, 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

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: 22570413
DOI: 10.1093/NAR/GKS355

Experimental method

X-RAY DIFFRACTION (1.95 Å)