A versatile partner of eukaryotic protein complexes that is involved in multiple biological processes: Kti11/Dph3.
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.
Bär
Christian
C
Biologicum, Institut für Genetik, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 10, D-06120 Halle (Saale), Germany.
Zabel
René
R
Liu
Shihui
S
Stark
Michael J R
MJ
Schaffrath
Raffael
R
D025141:Drug Resistance, Fungal; D015966:Gene Expression Regulation, Fungal; D006639:Histidine / Q000031:analogs & derivatives / Q000494:pharmacology; D007192:Indenes / Q000494:pharmacology; D055646:Killer Factors, Yeast; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009183:Mycotoxins / Q000494:pharmacology; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D012343:RNA, Transfer / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D007192:Indenes; C459979:KTI11 protein, S cerevisiae; D055646:Killer Factors, Yeast; D009183:Mycotoxins; D010445:Peptide Elongation Factors; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C058975:zymocin; C003329:sordarin; D006639:Histidine; C027527:diphthamide; D012343:RNA, Transfer; D008780:Methyltransferases; C076235:DPH5 protein, S cerevisiae