4Z4G

Human Argonaute2 Bound to t1-Inosine Target RNA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.181 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Water-mediated recognition of t1-adenosine anchors Argonaute2 to microRNA targets.

Schirle, N.T.Sheu-Gruttadauria, J.Chandradoss, S.D.Joo, C.MacRae, I.J.

(2015) Elife 4

  • DOI: https://doi.org/10.7554/eLife.07646
  • Primary Citation of Related Structures:  
    4Z4C, 4Z4D, 4Z4E, 4Z4F, 4Z4G, 4Z4H, 4Z4I

  • PubMed Abstract: 

    MicroRNAs (miRNAs) direct post-transcriptional regulation of human genes by guiding Argonaute proteins to complementary sites in messenger RNAs (mRNAs) targeted for repression. An enigmatic feature of many conserved mammalian miRNA target sites is that an adenosine (A) nucleotide opposite miRNA nucleotide-1 confers enhanced target repression independently of base pairing potential to the miRNA. In this study, we show that human Argonaute2 (Ago2) possesses a solvated surface pocket that specifically binds adenine nucleobases in the 1 position (t1) of target RNAs. t1A nucleotides are recognized indirectly through a hydrogen-bonding network of water molecules that preferentially interacts with the N6 amine on adenine. t1A nucleotides are not utilized during the initial binding of Ago2 to its target, but instead function by increasing the dwell time on target RNA. We also show that N6 adenosine methylation blocks t1A recognition, revealing a possible mechanism for modulation of miRNA target site potency.


  • Organizational Affiliation

    Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States.


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Protein argonaute-2859Homo sapiensMutation(s): 1 
Gene Names: AGO2EIF2C2
EC: 3.1.26
UniProt & NIH Common Fund Data Resources
Find proteins for Q9UKV8 (Homo sapiens)
Explore Q9UKV8 
Go to UniProtKB:  Q9UKV8
PHAROS:  Q9UKV8
GTEx:  ENSG00000123908 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9UKV8
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains LengthOrganismImage
RNA (5'-R(P*UP*UP*CP*AP*CP*AP*UP*UP*GP*CP*CP*CP*AP*AP*GP*UP*CP*UP*UP*U)-3')21synthetic construct
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains LengthOrganismImage
RNA (5'-R(*CP*AP*AP*UP*GP*UP*GP*A)-D(P*(IMP))-3')C [auth D]11synthetic construct
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.224 
  • R-Value Work: 0.179 
  • R-Value Observed: 0.181 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 55.663α = 90
b = 117.041β = 92.4
c = 70.104γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
SCALAdata scaling
PHENIXphasing

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 StatesGM104475

Revision History  (Full details and data files)

  • Version 1.0: 2015-09-23
    Type: Initial release
  • Version 1.1: 2017-09-20
    Changes: Author supporting evidence, Derived calculations
  • Version 1.2: 2019-12-25
    Changes: Author supporting evidence
  • Version 1.3: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description