Yeast Gene (alias ) Operates in the Initiation Step of Diphthamide Synthesis on Elongation Factor 2

Overview

Journal Microb Cell

Specialty Microbiology

Date 2023 Sep 4

PMID 37662670

Authors

Meike Arend

Koray Utkur

Harmen Hawer

Klaus Mayer

Namit Ranjan

Lorenz Adrian

Ulrich Brinkmann

Raffael Schaffrath

Affiliations

Soon will be listed here.

Abstract

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 network and an ill-defined function. On further examining the latter gene in yeast, we found that Δ 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 Δ 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 nomenclature indicating dual-functionality analogous to .

Citing Articles

Functional Integrity of Radical SAM Enzyme Dph1•Dph2 Requires Non-Canonical Cofactor Motifs with Tandem Cysteines.

Utkur K, Mayer K, Liu S, Brinkmann U, Schaffrath R Biomolecules. 2024; 14(4).

PMID: 38672486 PMC: 11048331. DOI: 10.3390/biom14040470.

Gene Mutations Identify a Candidate SAM Pocket in Radical Enzyme Dph1•Dph2 for Diphthamide Synthesis on EF2.

Utkur K, Schmidt S, Mayer K, Klassen R, Brinkmann U, Schaffrath R Biomolecules. 2023; 13(11).

PMID: 38002337 PMC: 10669111. DOI: 10.3390/biom13111655.

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