5KNN

Evolutionary gain of alanine mischarging to non-cognate tRNAs with a G4:U69 base pair


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.68 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.218 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Evolutionary Gain of Alanine Mischarging to Noncognate tRNAs with a G4:U69 Base Pair.

Sun, L.Gomes, A.C.He, W.Zhou, H.Wang, X.Pan, D.W.Schimmel, P.Pan, T.Yang, X.L.

(2016) J Am Chem Soc 138: 12948-12955

  • DOI: https://doi.org/10.1021/jacs.6b07121
  • Primary Citation of Related Structures:  
    5KNN

  • PubMed Abstract: 

    Fidelity of translation, which is predominately dictated by the accuracy of aminoacyl-tRNA synthetases in pairing amino acids with correct tRNAs, is of central importance in biology. Yet, deliberate modifications of translational fidelity can be beneficial. Here we found human and not E. coli AlaRS has an intrinsic capacity for mispairing alanine onto nonalanyl-tRNAs including tRNA Cys . Consistently, a cysteine-to-alanine substitution was found in a reporter protein expressed in human cells. All human AlaRS-mischarged tRNAs have a G4:U69 base pair in the acceptor stem. The base pair is required for the mischarging. By solving the crystal structure of human AlaRS and comparing it to that of E. coli AlaRS, we identified a key sequence divergence between eukaryotes and bacteria that influences mischarging. Thus, the expanded tRNA specificity of AlaRS appears to be an evolutionary gain-of-function to provide posttranscriptional alanine substitutions in eukaryotic proteins for potential regulations.


  • Organizational Affiliation

    Department of Cell and Molecular Biology, The Scripps Research Institute , La Jolla, California 92037, United States.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Alanine--tRNA ligase, cytoplasmic
A, B, C, D, E
A, B, C, D, E, F, G, H
450Homo sapiensMutation(s): 0 
Gene Names: AARS
EC: 6.1.1.7
UniProt & NIH Common Fund Data Resources
Find proteins for P49588 (Homo sapiens)
Explore P49588 
Go to UniProtKB:  P49588
PHAROS:  P49588
GTEx:  ENSG00000090861 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP49588
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.68 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.216 
  • R-Value Observed: 0.218 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 52.167α = 90.07
b = 98.26β = 89.95
c = 201.385γ = 90.11
Software Package:
Software NamePurpose
HKL-2000data collection
HKL-2000data scaling
REFMACrefinement
PDB_EXTRACTdata extraction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-09-28
    Type: Initial release
  • Version 1.1: 2016-10-19
    Changes: Database references
  • Version 1.2: 2023-09-27
    Changes: Data collection, Database references, Derived calculations, Refinement description