The Mycobacterium tuberculosis protein O-phosphorylation landscape.

Autor: Frando A; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA.; Department of Global Health, University of Washington, Seattle, WA, USA., Boradia V; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA., Gritsenko M; Pacific Northwest National Laboratory, Richland, WA, USA., Beltejar C; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA., Day L; Pacific Northwest National Laboratory, Richland, WA, USA., Sherman DR; Department of Microbiology, University of Washington, Seattle, WA, USA., Ma S; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA.; Department of Global Health, University of Washington, Seattle, WA, USA.; Department of Chemical Engineering, University of Washington, Seattle, WA, USA.; Department of Pediatrics, University of Washington, Seattle, WA, USA., Jacobs JM; Pacific Northwest National Laboratory, Richland, WA, USA., Grundner C; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA. Christoph.grundner@seattlechildrens.org.; Department of Global Health, University of Washington, Seattle, WA, USA. Christoph.grundner@seattlechildrens.org.; Department of Pediatrics, University of Washington, Seattle, WA, USA. Christoph.grundner@seattlechildrens.org.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2023 Mar; Vol. 8 (3), pp. 548-561. Date of Electronic Publication: 2023 Jan 23.
DOI: 10.1038/s41564-022-01313-7
Abstrakt: Bacterial phosphosignalling has been synonymous with two-component systems and their histidine kinases, but many bacteria, including Mycobacterium tuberculosis (Mtb), also code for Ser/Thr protein kinases (STPKs). STPKs are the main phosphosignalling enzymes in eukaryotes but the full extent of phosphorylation on protein Ser/Thr and Tyr (O-phosphorylation) in bacteria is untested. Here we explored the global signalling capacity of the STPKs in Mtb using a panel of STPK loss-of-function and overexpression strains combined with mass spectrometry-based phosphoproteomics. A deep phosphoproteome with >14,000 unique phosphosites shows that O-phosphorylation in Mtb is a vastly underexplored protein modification that affects >80% of the proteome and extensively interfaces with the transcriptional machinery. Mtb O-phosphorylation gives rise to an expansive, distributed and cooperative network of a complexity that has not previously been seen in bacteria and that is on par with eukaryotic phosphosignalling networks. A resource of >3,700 high-confidence direct substrate-STPK interactions and their transcriptional effects provides signalling context for >80% of Mtb proteins and allows the prediction and assembly of signalling pathways for mycobacterial physiology.
(© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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