4ZRA

CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS LPRG BINDING TO TRIACYLGLYCERIDE

Summary for 4ZRA

• Entry DOI: 10.2210/pdb4zra/pdb
• Related: 3MH8 3MHA
• Descriptor: Lipoprotein LprG, Tripalmitoylglycerol (3 entities in total)
• Functional Keywords: lprg, lipoprotein, structural genomics, tb structural genomics consortium, tbsgc, lipid binding protein
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Cellular location: Cell membrane ; Lipid-anchor : P9WK45
• Total number of polymer chains: 2
• Total formula weight: 43737.20

Authors

Martinot, A.J.,Farrow, M.,Bai, L.,Layre, E.,Cheng, T.Y.,Tsai, J.H.C.,Iqbal, J.,Annand, J.,Sullivan, Z.,Hussain, M.,Sacchettini, J.,Moody, D.B.,Seeliger, J.,Rubin, E.J.,TB Structural Genomics Consortium (TBSGC) (deposition date: 2015-05-12, release date: 2016-02-10, Last modification date: 2024-03-06)

Primary citation

Martinot, A.J.,Farrow, M.,Bai, L.,Layre, E.,Cheng, T.Y.,Tsai, J.H.,Iqbal, J.,Annand, J.W.,Sullivan, Z.A.,Hussain, M.M.,Sacchettini, J.,Moody, D.B.,Seeliger, J.C.,Rubin, E.J.
Mycobacterial Metabolic Syndrome: LprG and Rv1410 Regulate Triacylglyceride Levels, Growth Rate and Virulence in Mycobacterium tuberculosis.
Plos Pathog., 12:e1005351-e1005351, 2016

PubMed Abstract: Mycobacterium tuberculosis (Mtb) mutants lacking rv1411c, which encodes the lipoprotein LprG, and rv1410c, which encodes a putative efflux pump, are dramatically attenuated for growth in mice. Here we show that loss of LprG-Rv1410 in Mtb leads to intracellular triacylglyceride (TAG) accumulation, and overexpression of the locus increases the levels of TAG in the culture medium, demonstrating a role of this locus in TAG transport. LprG binds TAG within a large hydrophobic cleft and is sufficient to transfer TAG from donor to acceptor membranes. Further, LprG-Rv1410 is critical for broadly regulating bacterial growth and metabolism in vitro during carbon restriction and in vivo during infection of mice. The growth defect in mice is due to disrupted bacterial metabolism and occurs independently of key immune regulators. The in vivo essentiality of this locus suggests that this export system and other regulators of metabolism should be considered as targets for novel therapeutics.

PubMed: 26751071
DOI: 10.1371/journal.ppat.1005351

Experimental method

X-RAY DIFFRACTION (1.83 Å)