The protein kinase PknB negatively regulates biosynthesis and trafficking of mycolic acids in mycobacteria[S]
| Autor: | Virginie Molle, Alexandre Stella, Nicolas Tomas, Mamadou Daffé, Odile Burlet-Schiltz, Marie Locard-Paulet, Hedia Marrakchi, Nguyen-Hung Le |
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| Přispěvatelé: | Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, LPHI - Laboratory of Pathogen Host Interactions (LPHI), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
QD415-436 030204 cardiovascular system & hematology Protein Serine-Threonine Kinases Proteomics Biochemistry Dephosphorylation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology proteomics Biosynthesis Protein phosphorylation [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Protein kinase A Research Articles ComputingMilieux_MISCELLANEOUS biology phosphorylation Phosphoproteomics phosphoproteomics Biological Transport regulation Cell Biology Mycobacterium tuberculosis biology.organism_classification [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology 3. Good health Cell biology 030104 developmental biology chemistry Mycolic Acids Phosphorylation cell wall fatty acid Mycobacterium |
| Zdroj: | Journal of Lipid Research, Vol 61, Iss 8, Pp 1180-1191 (2020) Journal of Lipid Research Journal of Lipid Research, American Society for Biochemistry and Molecular Biology, 2020, 61 (8), pp.1180-1191. ⟨10.1194/jlr.RA120000747⟩ J Lipid Res |
| ISSN: | 0022-2275 |
| DOI: | 10.1194/jlr.RA120000747⟩ |
| Popis: | Mycobacterium tuberculosis is the causative agent of tuberculosis and remains one of the most widespread and deadliest bacterial pathogens in the world. A distinguishing feature of mycobacteria that sets them apart from other bacteria is the unique architecture of their cell wall, characterized by various species-specific lipids, most notably mycolic acids (MAs). Therefore, targeted inhibition of enzymes involved in MA biosynthesis, transport, and assembly has been extensively explored in drug discovery. Additionally, more recent evidence suggests that many enzymes in the MA biosynthesis pathway are regulated by kinase-mediated phosphorylation, thus opening additional drug-development opportunities. However, how phosphorylation regulates MA production remains unclear. Here, we used genetic strategies combined with lipidomics and phosphoproteomics approaches to investigate the role of protein phosphorylation in Mycobacterium. The results of this analysis revealed that the Ser/Thr protein kinase PknB regulates the export of MAs and promotes the remodeling of the mycobacterial cell envelope. In particular, we identified the essential MmpL3 as a substrate negatively regulated by PknB. Taken together, our findings add to the understanding of how PknB activity affects the mycobacterial MA biosynthesis pathway and reveal the essential role of protein phosphorylation/dephosphorylation in governing lipid metabolism, paving the way for novel antimycobacterial strategies. |
| Databáze: | OpenAIRE |
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