4A4I

Crystal structure of the human Lin28b cold shock domain


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.184 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

The Lin28 Cold-Shock Domain Remodels Pre-Let-7 Microrna.

Mayr, F.Schutz, A.Doge, N.Heinemann, U.

(2012) Nucleic Acids Res 40: 7492

  • DOI: https://doi.org/10.1093/nar/gks355
  • Primary Citation of Related Structures:  
    3ULJ, 4A4I, 4A75, 4A76, 4ALP

  • 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.


  • Organizational Affiliation

    Crystallography, Max-Delbrück Center for Molecular Medicine, Robert-Rössle Straße 10, 13125 Berlin, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEIN LIN-28 HOMOLOG B
A, B
90Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q6ZN17 (Homo sapiens)
Explore Q6ZN17 
Go to UniProtKB:  Q6ZN17
PHAROS:  Q6ZN17
GTEx:  ENSG00000187772 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6ZN17
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.184 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 46.181α = 90
b = 62.477β = 90
c = 77.318γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-08-08
    Type: Initial release
  • Version 1.1: 2012-09-05
    Changes: Database references
  • Version 1.2: 2024-05-08
    Changes: Data collection, Database references, Derived calculations, Other