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A protein adaptor mediating Ap4A-dependent control of protein acetylation.

ABSTRACT: Reversible lysine acetylation is a highly conserved post-translational modification across all domains of life, modulating diverse cellular processes. However, the regulatory mechanisms governing this modification remain poorly understood. Here, we uncover a novel regulatory system in Bacillus subtilis involving the histone deacetylase (HDAC)-like protein AcuC, which targets multiple substrates, including acetyl-CoA synthetase and translation elongation factor. We show that AcuC is inhibited through complex formation with AcuB, a previously uncharacterized protein. We further demonstrate that the alarmone diadenosine tetraphosphate (Ap4A) binds to the cystathionine beta-synthase (CBS) domain of AcuB, stabilizing the AcuB-AcuC complex and enhancing AcuC inhibition. This study identify AcuB as an Ap4A-enhanced deacetylation inhibitor, revealing a new regulatory mechanism for HDAC-like proteins. Our findings also provide the first direct evidence that the secondary messenger Ap4A modulates protein (de)acetylation, highlighting a regulatory network linking cell stress, proteome acetylation, and acetyl-CoA availability. These insights advance our understanding of protein acetylation control.

INSTRUMENT(S):

ORGANISM(S): Geobacillus Thermodenitrificans Ng80-2

SUBMITTER: Wieland Steinchen

LAB HEAD: Gert Bange

PROVIDER: PXD064203 | Pride | 2026-01-21

REPOSITORIES: Pride

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			Action	DRS
	230511_HX_485_Ba_AcuB-AcuC-Ap4A.zip	Other
	230511_HX_485_Ba_AcuB-AcuC.zip	Other
	230511_HX_485_Ba_AcuB-Ap4A.zip	Other
	230511_HX_485_Ba_AcuB.DnX	Other
	230511_HX_485_Ba_AcuB.zip	Other

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