Dataset Information

A quantitative proteomics approach to monitor targeted protein degradation in M. smegmatis

ABSTRACT: Targeted protein degradation via the ubiquitin proteasome has been established in eukaryotes, however no application has been shown in bacteria so far. In the present work, selective protein degradation is shown using hetero bifunctional drugs, bringing substrates in close proximity to the bacterial ClpC1P1P2 protein degradation complex. We performed a TMT based quantitative proteomics analysis to monitor degradation of human BRDT in Mycobacterium smegmatis. Our data shows selective degradation of BRDT when using bacterial PROTACS, indicating the first successful application of targeted protein degradation in bacteria.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Mycobacterium Smegmatis (strain Atcc 700084 / Mc(2)155) Bacteria

SUBMITTER: David Hoi

LAB HEAD: Markus Hartl

PROVIDER: PXD021505 | Pride | 2022-08-12

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	2019.05_UP000000757_Mycobacterium_smegmatis_all_BRDT.fasta	Fasta
	20200424_QExHFX1_RSLC1_Hoi_Clausen_IMP_Msm_tmt_rep1_frac.msf	Msf
	20200424_QExHFX1_RSLC1_Hoi_Clausen_IMP_Msm_tmt_rep1_frac1.raw	Raw
	20200424_QExHFX1_RSLC1_Hoi_Clausen_IMP_Msm_tmt_rep1_frac10.raw	Raw
	20200424_QExHFX1_RSLC1_Hoi_Clausen_IMP_Msm_tmt_rep1_frac2.raw	Raw

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Publications

BacPROTACs mediate targeted protein degradation in bacteria.

Morreale Francesca E FE Kleine Stefan S Leodolter Julia J Junker Sabryna S Hoi David M DM Ovchinnikov Stepan S Okun Anastasia A Kley Juliane J Kurzbauer Robert R Junk Lukas L Guha Somraj S Podlesainski David D Kazmaier Uli U Boehmelt Guido G Weinstabl Harald H Rumpel Klaus K Schmiedel Volker M VM Hartl Markus M Haselbach David D Meinhart Anton A Kaiser Markus M Clausen Tim T

Cell 20220603 13

Hijacking the cellular protein degradation system offers unique opportunities for drug discovery, as exemplified by proteolysis-targeting chimeras. Despite their great promise for medical chemistry, so far, it has not been possible to reprogram the bacterial degradation machinery to interfere with microbial infections. Here, we develop small-molecule degraders, so-called BacPROTACs, that bind to the substrate receptor of the ClpC:ClpP protease, priming neo-substrates for degradation. In addition ...[more]

PMID: 35662409

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