Turapov, Obolbek, Forti, Francesca, Kadhim, Baleegh, Ghisotti, Daniela, Sassine, Jad, Straatman-Iwanowska, Anna, Bottrill, Andrew R, Moynihan, Patrick J, Wallis, Russell, Barthe, Philippe et al (show 4 more authors)
(2018)
Two Faces of CwIM, an Essential PknB Substrate, in Mycobacterium tuberculosis.
CELL REPORTS, 25 (1).
57-+.
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Abstract
Tuberculosis claims >1 million lives annually, and its causative agent Mycobacterium tuberculosis is a highly successful pathogen. Protein kinase B (PknB) is reported to be critical for mycobacterial growth. Here, we demonstrate that PknB-depleted M. tuberculosis can replicate normally and can synthesize peptidoglycan in an osmoprotective medium. Comparative phosphoproteomics of PknB-producing and PknB-depleted mycobacteria identify CwlM, an essential regulator of peptidoglycan synthesis, as a major PknB substrate. Our complementation studies of a cwlM mutant of M. tuberculosis support CwlM phosphorylation as a likely molecular basis for PknB being essential for mycobacterial growth. We demonstrate that growing mycobacteria produce two forms of CwlM: a non-phosphorylated membrane-associated form and a PknB-phosphorylated cytoplasmic form. Furthermore, we show that the partner proteins for the phosphorylated and non-phosphorylated forms of CwlM are FhaA, a fork head-associated domain protein, and MurJ, a proposed lipid II flippase, respectively. From our results, we propose a model in which CwlM potentially regulates both the biosynthesis of peptidoglycan precursors and their transport across the cytoplasmic membrane.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Cell Wall, Mycobacterium tuberculosis, N-Acetylmuramoyl-L-alanine Amidase, Amino Acid Sequence, Phosphorylation, Proto-Oncogene Proteins c-akt |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 31 Mar 2022 07:39 |
| Last Modified: | 18 Jan 2023 21:06 |
| DOI: | 10.1016/j.celrep.2018.09.004 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3151772 |
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