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. 2021 Feb;115(2):208-221.
doi: 10.1111/mmi.14611. Epub 2020 Nov 3.

Identification of residues important for M. tuberculosis MmpL11 function reveals that function is modulated by phosphorylation in the C-terminal domain

Geoff C Melly  1 , Haley Stokas  1 , Patrick M Davidson  1 , José Santinni Roma  1 , Heather L Rhodes  1 , Georgiana E Purdy  1
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Free article

Identification of residues important for M. tuberculosis MmpL11 function reveals that function is modulated by phosphorylation in the C-terminal domain

Geoff C Melly et al. Mol Microbiol. 2021 Feb.
Free article

Abstract

The Mycobacterium tuberculosis cell envelope is a critical interface between the host and pathogen and provides a protective barrier against the immune response and antibiotics. Cell envelope lipids are also mycobacterial virulence factors that influence the host immune response. The mycobacterial membrane protein large (MmpL) proteins transport cell envelope lipids and siderophores that are important for the basic physiology and pathogenesis of M. tuberculosis. We recently identified MmpL11 as a conserved transporter of mycolic acid-containing lipids including monomeromycolyl diacylglycerol (MMDAG), mycolate wax ester (MWE), and long-chain triacylglycerols (LC-TAGs). These lipids contribute to biofilm formation in M. tuberculosis and M. smegmatis, and non-replicating persistence in M. tuberculosis. In this report, we identified domains and residues that are essential for MmpL11TB lipid transporter activity. Specifically, we show that the D1 periplasmic loop and a conserved tyrosine are essential for the MmpL11 function. Intriguingly, we found that MmpL11 levels are regulated by the phosphorylation of threonine in the cytoplasmic C-terminal domain, providing the first direct evidence of the phospho-regulation of MmpL11 transporter activity in M. tuberculosis and M. smegmatis. Our results offer further insight into the function of MmpL transporters and regulation of mycobacterial cell envelope biogenesis.

Keywords: Mycobacterium tuberculosis; MmpL transporter; biofilm; mycolic acid; serine-threonine protein kinase.

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REFERENCES

    1. Backus, K.M., Dolan, M.A., Barry, C.S., Joe, M., McPhie, P., Boshoff, H.I.M., et al. (2014) The three Mycobacterium tuberculosis antigen 85 isoforms have unique substrates and activities determined by non-active site regions. Journal of Biological Chemistry, 289, 25041-25053.
    1. Bah, A. and Forman-Kay, J.D. (2016) Modulation of intrinsically disordered protein function by post-translational modifications. Journal of Biological Chemistry, 291, 6696-6705.
    1. Barry, C.E., Lee, R.E., Mdluli, K., Sampson, A.E., Schroeder, B.G., Slayden, R.A., et al. (1998) Mycolic acids: structure, biosynthesis and physiological functions. Progress in Lipid Research, 37, 143-179. http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id...
    1. Belisle, J.T., Vissa, V.D., Sievert, T., Takayama, K., Brennan, P.J. and Besra, G.S. (1997) Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis. Science, 276, 1420-1422.
    1. Bernut, A., Viljoen, A., Dupont, C., Sapriel, G., Blaise, M., Bouchier, C., et al. (2015) Insights into the smooth-to-rough transitioning in Mycobacterium bolletii unravels a functional Tyr residue conserved in all mycobacterial MmpL family members. Molecular Microbiology, 99, n/a-n/a.

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