A versatile partner of eukaryotic protein complexes that is involved in multiple biological processes: Kti11/Dph3

Christian Baer, Rene Zabel, Shihui Liu, Michael J. R. Stark, Raffael Schaffrath

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    40 Citations (Scopus)

    Abstract

    The Kluyveromyces lactis killer toxin zymocin insensitive 11 (KTI11) gene from Saccharomyces cerevisiae is allelic with the diphthamide synthesis 3 (DPH3) locus. Here, we present evidence that the KTI11 gene product is a versatile partner of proteins and operates in multiple biological processes. Notably, Kti11 immune precipitates contain Elp2 and Elp5, two subunits of the Elongator complex which is involved in transcription, tRNA modification and zymocin toxicity. KTI11 deletion phenocopies Elongator-minus cells and causes antisuppression of nonsense and missense suppressor tRNAs (SUP4, SOE1), zymocin resistance and protection against the tRNase attack of zymocin. In addition and unlike Elongator mutants, kti11 mutants resist diphtheria toxin (DT), protect against ADP-ribosylation of eukaryotic translation elongation factor 2 (eEF2) by DT and induce resistance against sordarin, an eEF2 poisoning antifungal. The latter phenotype applies to all diphthamide mutants (dph1-dph5) tested and Kti11/Dph3 physically interacts with diphthamide synthesis factors Dph1 and Dph2, presumably as part of a trimeric complex. Moreover, we present a separation of function mutation in KTI11, kti11-1, which dissociates zymocin resistance from DT sensitivity. It encodes a C-terminal Kti11 truncation that almost entirely abolishes Elongator interaction without affecting association with Kti13, another Kti11 partner protein.

    Original languageEnglish
    Pages (from-to)1221-1233
    Number of pages13
    JournalMolecular Microbiology
    Volume69
    Issue number5
    DOIs
    Publication statusPublished - Sep 2008

    Keywords

    • KLUYVEROMYCES-LACTIS ZYMOCIN
    • SACCHAROMYCES-CEREVISIAE REVEALS
    • ADP-RIBOSYLATING TOXINS
    • DIPHTHERIA-TOXIN
    • TRANSFER-RNA
    • TRANSLATION ELONGATION-FACTOR-2
    • ELONGATOR COMPLEX
    • TRANSCRIPTIONAL ELONGATION
    • DIPHTHAMIDE BIOSYNTHESIS
    • GAMMA-TOXIN

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