7KX9

Cryo-EM structure of Ephydatia fluviatilis PiwiA-piRNA-target complex


Experimental Data Snapshot

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.50 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structural basis for piRNA targeting.

Anzelon, T.A.Chowdhury, S.Hughes, S.M.Xiao, Y.Lander, G.C.MacRae, I.J.

(2021) Nature 597: 285-289

  • DOI: https://doi.org/10.1038/s41586-021-03856-x
  • Primary Citation of Related Structures:  
    7KX7, 7KX9

  • PubMed Abstract: 

    PIWI proteins use PIWI-interacting RNAs (piRNAs) to identify and silence transposable elements and thereby maintain genome integrity between metazoan generations 1 . The targeting of transposable elements by PIWI has been compared to mRNA target recognition by Argonaute proteins 2,3 , which use microRNA (miRNA) guides, but the extent to which piRNAs resemble miRNAs is not known. Here we present cryo-electron microscopy structures of a PIWI-piRNA complex from the sponge Ephydatia fluviatilis with and without target RNAs, and a biochemical analysis of target recognition. Mirroring Argonaute, PIWI identifies targets using the piRNA seed region. However, PIWI creates a much weaker seed so that stable target association requires further piRNA-target pairing, making piRNAs less promiscuous than miRNAs. Beyond the seed, the structure of PIWI facilitates piRNA-target pairing in a manner that is tolerant of mismatches, leading to long-lived PIWI-piRNA-target interactions that may accumulate on transposable-element transcripts. PIWI ensures targeting fidelity by physically blocking the propagation of piRNA-target interactions in the absence of faithful seed pairing, and by requiring an extended piRNA-target duplex to reach an endonucleolytically active conformation. PIWI proteins thereby minimize off-targeting cellular mRNAs while defending against evolving genomic threats.


  • Organizational Affiliation

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.


Macromolecules

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Piwi-A768Ephydatia fluviatilisMutation(s): 0 
Gene Names: EfPiwiA
UniProt
Find proteins for D5MRY8 (Ephydatia fluviatilis)
Explore D5MRY8 
Go to UniProtKB:  D5MRY8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupD5MRY8
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains LengthOrganismImage
RNA (5'-R(P*UP*CP*UP*CP*UP*UP*GP*AP*GP*UP*UP*GP*GP*AP*CP*AP*AP*AP*UP*GP*GP*CP*AP*(OMG))-3')24synthetic construct
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains LengthOrganismImage
RNA (5'-R(P*UP*GP*UP*CP*CP*AP*AP*CP*UP*CP*AP*AP*GP*AP*GP*A)-3')16synthetic construct
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: ELECTRON MICROSCOPY
  • Resolution: 3.50 Å
  • Aggregation State: PARTICLE 
  • Reconstruction Method: SINGLE PARTICLE 
EM Software:
TaskSoftware PackageVersion
RECONSTRUCTIONRELION2.0

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)United States--

Revision History  (Full details and data files)

  • Version 1.0: 2021-07-14
    Type: Initial release
  • Version 1.1: 2021-09-01
    Changes: Database references
  • Version 1.2: 2021-09-15
    Changes: Database references
  • Version 1.3: 2021-09-22
    Changes: Database references
  • Version 1.4: 2024-05-29
    Changes: Data collection