Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamide synthesis on elongation factor 2
In yeast, Elongator-dependent tRNA modifications are regulated by the Kti11•Kti13 dimer and hijacked for cell killing by zymocin, a tRNase ribotoxin. Kti11 (alias Dph3) also controls modification of elongation factor 2 (EF2) with diphthamide, the target for lethal ADP-ribosylation by diphtheria toxi...
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Shared Science Publishers OG
2022-08-01
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| Series: | Microbial Cell |
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| Online Access: | http://microbialcell.com/researcharticles/2023a-arend-microbial-cell/ |
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| author | Meike Arend Koray Ütkür Harmen Hawer Klaus Mayer Namit Ranjan Lorenz Adrian Ulrich Brinkmann Raffael Schaffrath |
| author_facet | Meike Arend Koray Ütkür Harmen Hawer Klaus Mayer Namit Ranjan Lorenz Adrian Ulrich Brinkmann Raffael Schaffrath |
| author_sort | Meike Arend |
| collection | DOAJ |
| description | In yeast, Elongator-dependent tRNA modifications are regulated by the Kti11•Kti13 dimer and hijacked for cell killing by zymocin, a tRNase ribotoxin. Kti11 (alias Dph3) also controls modification of elongation factor 2 (EF2) with diphthamide, the target for lethal ADP-ribosylation by diphtheria toxin (DT). Diphthamide formation on EF2 involves four biosynthetic steps encoded by the DPH1-DPH7 network and an ill-defined KTI13 function. On further examining the latter gene in yeast, we found that kti13Δ null-mutants maintain unmodified EF2 able to escape ADP-ribosylation by DT and to survive EF2 inhibition by sordarin, a diphthamide-dependent antifungal. Consistently, mass spectrometry shows kti13Δ cells are blocked in proper formation of amino-carboxyl-propyl-EF2, the first diphthamide pathway intermediate. Thus, apart from their common function in tRNA modification, both Kti11/Dph3 and Kti13 share roles in the initiation step of EF2 modification. We suggest an alias KTI13/DPH8 nomenclature indicating dual-functionality analogous to KTI11/DPH3. |
| format | Article |
| id | doaj-art-cbab6fc1de5a40b2b53aba41197cf186 |
| institution | DOAJ |
| issn | 2311-2638 |
| language | English |
| publishDate | 2022-08-01 |
| publisher | Shared Science Publishers OG |
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| series | Microbial Cell |
| spelling | doaj-art-cbab6fc1de5a40b2b53aba41197cf1862025-08-20T02:57:39ZengShared Science Publishers OGMicrobial Cell2311-26382022-08-0110919520310.15698/mic2023.09.804Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamide synthesis on elongation factor 2Meike Arend0Koray Ütkür1Harmen Hawer2Klaus Mayer3Namit Ranjan4Lorenz Adrian5Ulrich Brinkmann6Raffael Schaffrath7Institute of Biology, Division of Microbiology, University of Kassel, Heinrich-Plett-Str. 40, 34132 Kassel, Germany.Institute of Biology, Division of Microbiology, University of Kassel, Heinrich-Plett-Str. 40, 34132 Kassel, Germany.Institute of Biology, Division of Microbiology, University of Kassel, Heinrich-Plett-Str. 40, 34132 Kassel, Germany.Roche Pharma Research and Early Development, Large Molecule Research, Roche Innovation Center München, Nonnenwald 2, 82377 Penzberg, Germany.Max-Planck-Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.Environmental Biotechnology, Helmholtz Centre for Environmental Research - UFZ, 04318 Leipzig, Germany.Roche Pharma Research and Early Development, Large Molecule Research, Roche Innovation Center München, Nonnenwald 2, 82377 Penzberg, Germany.Institute of Biology, Division of Microbiology, University of Kassel, Heinrich-Plett-Str. 40, 34132 Kassel, Germany.In yeast, Elongator-dependent tRNA modifications are regulated by the Kti11•Kti13 dimer and hijacked for cell killing by zymocin, a tRNase ribotoxin. Kti11 (alias Dph3) also controls modification of elongation factor 2 (EF2) with diphthamide, the target for lethal ADP-ribosylation by diphtheria toxin (DT). Diphthamide formation on EF2 involves four biosynthetic steps encoded by the DPH1-DPH7 network and an ill-defined KTI13 function. On further examining the latter gene in yeast, we found that kti13Δ null-mutants maintain unmodified EF2 able to escape ADP-ribosylation by DT and to survive EF2 inhibition by sordarin, a diphthamide-dependent antifungal. Consistently, mass spectrometry shows kti13Δ cells are blocked in proper formation of amino-carboxyl-propyl-EF2, the first diphthamide pathway intermediate. Thus, apart from their common function in tRNA modification, both Kti11/Dph3 and Kti13 share roles in the initiation step of EF2 modification. We suggest an alias KTI13/DPH8 nomenclature indicating dual-functionality analogous to KTI11/DPH3.http://microbialcell.com/researcharticles/2023a-arend-microbial-cell/budding yeastef2 diphthamide modificationdiphtheria toxintrna modificationelongatortrnase zymocin |
| spellingShingle | Meike Arend Koray Ütkür Harmen Hawer Klaus Mayer Namit Ranjan Lorenz Adrian Ulrich Brinkmann Raffael Schaffrath Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamide synthesis on elongation factor 2 Microbial Cell budding yeast ef2 diphthamide modification diphtheria toxin trna modification elongator trnase zymocin |
| title | Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamide synthesis on elongation factor 2 |
| title_full | Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamide synthesis on elongation factor 2 |
| title_fullStr | Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamide synthesis on elongation factor 2 |
| title_full_unstemmed | Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamide synthesis on elongation factor 2 |
| title_short | Yeast gene KTI13 (alias DPH8) operates in the initiation step of diphthamide synthesis on elongation factor 2 |
| title_sort | yeast gene kti13 alias dph8 operates in the initiation step of diphthamide synthesis on elongation factor 2 |
| topic | budding yeast ef2 diphthamide modification diphtheria toxin trna modification elongator trnase zymocin |
| url | http://microbialcell.com/researcharticles/2023a-arend-microbial-cell/ |
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