A Single Regulator NrtR Controls Bacterial NAD Homeostasis Via Its Acetylation

Overview

Journal Elife

Specialty Biology

Date 2019 Oct 10

PMID 31596237

Citations 9

Authors

Rongsui Gao

Wenhui Wei

Bachar H Hassan

Jun Li

Jiaoyu Deng

Youjun Feng

Affiliations

Soon will be listed here.

Abstract

Nicotinamide adenine dinucleotide (NAD) is an indispensable cofactor in all domains of life, and its homeostasis must be regulated tightly. Here we report that a Nudix-related transcriptional factor, designated MsNrtR (MSMEG_3198), controls the pathway of NADbiosynthesis in , a non-tuberculosis . The integrated evidence and confirms that MsNrtR is an auto-repressor, which negatively controls the NADbiosynthetic pathway. Binding of MsNrtR cognate DNA is finely mapped, and can be disrupted by an ADP-ribose intermediate. Unexpectedly, we discover that the acetylation of MsNrtR at Lysine 134 participates in the homeostasis of intra-cellular NAD level in . Furthermore, we demonstrate that NrtR acetylation proceeds via the non-enzymatic acetyl-phosphate (AcP) route rather than by the enzymatic Pat/CobB pathway. In addition, the acetylation also occurs on the paralogs of NrtR in the Gram-positive bacterium and the Gram-negative bacterium , suggesting that these proteins have a common mechanism of post-translational modification in the context of NAD homeostasis. Together, these findings provide a first paradigm for the recruitment of acetylated NrtR to regulate bacterial central NAD metabolism.

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