DOE OSTI · 1997397
The Mycobacterium tuberculosis protein O -phosphorylation landscape
Abstract
Bacterial phosphosignaling has long been synonymous with the histidine kinases of the two component systems (TCSs), but many bacteria, including Mycobacterium tuberculosis (Mtb), also code for Ser/Thr protein kinases (STPKs). STPKs are the main phosphosignaling enzymes in eukaryotes, but the full extent of phosphorylation on protein Ser/Thr and Tyr (O-phosphorylation) in bacteria is unclear. Here, we explored the global signaling capacity of the STPKs in Mtb. We generated a panel of STPK loss- and gain-of-function strains and measured the resulting O-phosphorylation and transcriptional changes. This deep phosphoproteome shows that O-phosphorylation in Mtb is a vastly underexplored protein modification that affects >70% of the proteome. The substrate-kinase interactions of STPKs show an extensive interface with the transcriptional machinery, resulting in STPK regulation of gene expression of over 30% of Mtb genes. Finally, Mtb O-phosphorylation gives rise to an expansive, distributed, and cooperative network of a complexity that has previously only been associated with eukaryotic phosphosignaling networks.
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Frando, Andrew, Boradia, Vishant, Gritsenko, Marina, Beltejar, Michael-Claude, Day, Le Z., Sherman, David R., Ma, Shuyi, Jacobs, Jon M., Grundner, Christoph. 2023-01-23. The Mycobacterium tuberculosis protein O -phosphorylation landscape. https://doi.org/10.1038/s41564-022-01313-7
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