4A76: The Lin28b Cold shock domain in complex with heptathymidine

Citation:
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.
PDB ID: 4A76Download
MMDB ID: 102688
PDB Deposition Date: 2011/11/11
Updated in MMDB: 2012/09
Experimental Method:
x-ray diffraction
Resolution: 1.92  Å
Source Organism:
Xenopus tropicalis
Similar Structures:
Biological Unit for 4A76: dimeric; determined by author and by software (PISA)
Molecular Components in 4A76
Label Count Molecule
Protein (1 molecule)
1
Lin28 Cold Shock Domain
Molecule annotation
Nucleotide(1 molecule)
1
5'-d(*tp*tp*tp*tp*tp*tp*tp)-3'
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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