Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2016 May 27;291(22):11911-27. doi: 10.1074/jbc.M116.725390. Epub 2016 Apr 1.

Structural Divergence of the Group I Intron Binding Surface in Fungal Mitochondrial Tyrosyl-tRNA Synthetases That Function in RNA Splicing.

Author information

1
From the Institute for Cellular and Molecular Biology and Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas 78712 and.
2
Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742.
3
From the Institute for Cellular and Molecular Biology and Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas 78712 and lambowitz@austin.utexas.edu.

Abstract

The mitochondrial tyrosyl-tRNA synthetases (mtTyrRSs) of Pezizomycotina fungi, a subphylum that includes many pathogenic species, are bifunctional proteins that both charge mitochondrial tRNA(Tyr) and act as splicing cofactors for autocatalytic group I introns. Previous studies showed that one of these proteins, Neurospora crassa CYT-18, binds group I introns by using both its N-terminal catalytic and C-terminal anticodon binding domains and that the catalytic domain uses a newly evolved group I intron binding surface that includes an N-terminal extension and two small insertions (insertions 1 and 2) with distinctive features not found in non-splicing mtTyrRSs. To explore how this RNA binding surface diverged to accommodate different group I introns in other Pezizomycotina fungi, we determined x-ray crystal structures of C-terminally truncated Aspergillus nidulans and Coccidioides posadasii mtTyrRSs. Comparisons with previous N. crassa CYT-18 structures and a structural model of the Aspergillus fumigatus mtTyrRS showed that the overall topology of the group I intron binding surface is conserved but with variations in key intron binding regions, particularly the Pezizomycotina-specific insertions. These insertions, which arose by expansion of flexible termini or internal loops, show greater variation in structure and amino acids potentially involved in group I intron binding than do neighboring protein core regions, which also function in intron binding but may be more constrained to preserve mtTyrRS activity. Our results suggest a structural basis for the intron specificity of different Pezizomycotina mtTyrRSs, highlight flexible terminal and loop regions as major sites for enzyme diversification, and identify targets for therapeutic intervention by disrupting an essential RNA-protein interaction in pathogenic fungi.

KEYWORDS:

RNA binding protein; aminoacyl tRNA synthetase; protein evolution; ribozyme; x-ray crystallography

PMID:
27036943
PMCID:
PMC4882457
DOI:
10.1074/jbc.M116.725390
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center