Back to Search Start Over

Mutations in ribosomal protein L10e confer resistance to the fungal-specific eukaryotic elongation factor 2 inhibitor sordarin.

Authors :
Justice MC
Ku T
Hsu MJ
Carniol K
Schmatz D
Nielsen J
Source :
The Journal of biological chemistry [J Biol Chem] 1999 Feb 19; Vol. 274 (8), pp. 4869-75.
Publication Year :
1999

Abstract

The natural product sordarin, a tetracyclic diterpene glycoside, selectively inhibits fungal protein synthesis by impairing the function of eukaryotic elongation factor 2 (eEF2). Sordarin and its derivatives bind to the eEF2-ribosome-nucleotide complex in sensitive fungi, stabilizing the post-translocational GDP form. We have previously described a class of Saccharomyces cerevisiae mutants that exhibit resistance to varying levels of sordarin and have identified amino acid substitutions in yeast eEF2 that confer sordarin resistance. We now report on a second class of sordarin-resistant mutants. Biochemical and molecular genetic analysis of these mutants demonstrates that sordarin resistance is dependent on the essential large ribosomal subunit protein L10e in S. cerevisiae. Five unique L10e alleles were characterized and sequenced, and several nucleotide changes that differ from the wild-type sequence were identified. Changes that result in the resistance phenotype map to 4 amino acid substitutions and 1 amino acid deletion clustered in a conserved 10-amino acid region of L10e. Like the previously identified eEF2 mutations, the mutant ribosomes show reduced sordarin-conferred stabilization of the eEF2-nucleotide-ribosome complex. To our knowledge, this report provides the first description of ribosomal protein mutations affecting translocation. These results and our previous observations with eEF2 suggest a functional linkage between L10e and eEF2.

Details

Language :
English
ISSN :
0021-9258
Volume :
274
Issue :
8
Database :
MEDLINE
Journal :
The Journal of biological chemistry
Publication Type :
Academic Journal
Accession number :
9988728
Full Text :
https://doi.org/10.1074/jbc.274.8.4869