5UZZ

Structure of wild type pre-miR21 apical loop


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

A Macrocyclic Peptide Ligand Binds the Oncogenic MicroRNA-21 Precursor and Suppresses Dicer Processing.

Shortridge, M.D.Walker, M.J.Pavelitz, T.Chen, Y.Yang, W.Varani, G.

(2017) ACS Chem Biol 12: 1611-1620

  • DOI: https://doi.org/10.1021/acschembio.7b00180
  • Primary Citation of Related Structures:  
    5UZT, 5UZZ

  • PubMed Abstract: 

    MicroRNAs (miRNAs) help orchestrate cellular growth and survival through post-transcriptional mechanisms. The dysregulation of miRNA biogenesis can lead to cellular growth defects and chemotherapeutic resistance and plays a direct role in the development of many chronic diseases. Among these RNAs, miR-21 is consistently overexpressed in most human cancers, leading to the down-regulation of key tumor-suppressing and pro-apoptotic factors, suggesting that inhibition of miR-21 biogenesis could reverse these negative effects. However, targeted inhibition of miR-21 using small molecules has had limited success. To overcome difficulties in targeting RNA secondary structure with small molecules, we developed a class of cyclic β-hairpin peptidomimetics which bind to RNA stem-loop structures, such as miRNA precursors, with potent affinity and specificity. We screened an existing cyclic peptide library and discovered a lead structure which binds to pre-miR21 with K D = 200 nM and prefers it over other pre-miRNAs. The NMR structure of the complex shows that the peptide recognizes the Dicer cleavage site and alters processing of the precursor to the mature miRNA in vitro and in cultured cells. The structure provides a rationale for the peptide binding activity and clear guidance for further improvements in affinity and targeting.


  • Organizational Affiliation

    Department of Chemistry, University of Washington, Seattle , Box 351700, Seattle, Washington 98195, United States.


Macromolecules

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
14-mer Peptide14synthetic constructMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Find similar nucleic acids by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains LengthOrganismImage
pre-miR2131Homo sapiens
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 10 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United StatesRO1 GM103834
American Cancer SocietyUnited StatesPF-13-056-01-RMC

Revision History  (Full details and data files)

  • Version 1.0: 2017-06-14
    Type: Initial release
  • Version 1.1: 2017-06-28
    Changes: Database references
  • Version 1.2: 2017-09-13
    Changes: Author supporting evidence
  • Version 1.3: 2020-01-01
    Changes: Author supporting evidence, Data collection
  • Version 1.4: 2023-06-14
    Changes: Database references, Other