Evidence that Protein Antigen b of Mycobacterium Tuberculosis is Involved in Phosphate Metabolism

Andersen, Åse Bengård; Ljungqvist, L; Olsen, Marianne

doi:10.1099/00221287-136-3-477

Cited by 58 publications

(39 citation statements)

References 19 publications

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“…The 38-kDa PstS-1, LpqH, 27-kDa LprA, and LprG are major lipoproteins found in the M. tuberculosis cell wall. PstS-1 is a transporter of inorganic phosphate, and was identified as a M. tuberculosis complex-specific marker and immunodominant target of the human immune response (33)(34)(35)(36). The 19-kDa LpqH has no known function but is a TLR-2 agonist and target of the human immune response (17,37,38).…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosisLprG (Rv1411c): A Novel TLR-2 Ligand That Inhibits Human Macrophage Class II MHC Antigen Processing

Gehring

Dobos

Belisle

et al. 2004

The Journal of Immunology

227

193

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MHC class II (MHC-II)-restricted CD4+ T cells are essential for control of Mycobacterium tuberculosis infection. This report describes the identification and purification of LprG (Rv1411c) as an inhibitor of primary human macrophage MHC-II Ag processing. LprG is a 24-kDa lipoprotein found in the M. tuberculosis cell wall. Prolonged exposure (>16 h) of human macrophages to LprG resulted in marked inhibition of MHC-II Ag processing. Inhibition of MHC-II Ag processing was dependent on TLR-2. Short-term exposure (<6 h) to LprG stimulated TLR-2-dependent TNF-α production. Thus, LprG can exploit TLR-2 signaling to inhibit MHC-II Ag processing in human macrophages. Inhibition of MHC-II Ag processing by mycobacterial lipoproteins may allow M. tuberculosis, within infected macrophages, to avoid recognition by CD4+ T cells.

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Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosisLprG (Rv1411c): A Novel TLR-2 Ligand That Inhibits Human Macrophage Class II MHC Antigen Processing

Gehring

Dobos

Belisle

et al. 2004

The Journal of Immunology

227

193

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“…First, peptide bonds within this segment, (a) in the isolated domain I proteins of R. rubrum and E. coli transhydrogenase [40], B. sphaericus [40], B. subtilis [41], Mycobacterium tuberculosis [42]; transhydrogenases (TH), E. coli [S], Bovis [9], R. rubrum [ll], Eimeria tenella [lo]. The numbers in parenthesis refer to the first and last amino acid residues in the sequences shown, as predicted from the nucleotide sequence of the genes or cDNA.…”

Section: Discussionmentioning

confidence: 99%

Conformational Dynamics of a Mobile Loop in the NAD(H)‐Binding Subunit of Proton‐Translocating Transhydrogenases from Rhodospirillum Rubrum and Escherichia Coli

Diggle¹,

Cotton²,

Grimley³

et al. 1995

European Journal of Biochemistry

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Transhydrogenase catalyses the reversible transfer of reducing equivalents between NAD(H) and NADP(H) to the translocation of protons across a membrane. Uniquely in Rhodospirillum rubrum, the NAD(H)-binding subunit (called Th,) exists as a separate subunit which can be reversibly dissociated from the membrane-located subunits. We have expressed the gene for R. rubrum Th, in Escherichia coli to yield large quantities of protein. Low concentrations of either trypsin or endoproteinase Lys-C lead to cleavage of purified Th, specifically at Lys227-Thr228 and Lys237-Glu238. Observations on the onedimensional 'H-NMR spectra of Th, before and after proteolysis indicate that the segment which straddles the cleavage sites forms a mobile loop protruding from the surface of the protein. Alanine dehydrogenase, which is very similar in sequence to the NAD(H)-binding subunit of transhydrogenase, lacks this segment. Limited proteolytic cleavage has little effect on some of the structural characteristics of Th, (its dimeric nature, its ability to bind to the membrane-located subunits of transhydrogenase, and the short-wavelength fluorescence emission of a unique Trp residue) but does decrease the NADH-binding affinity, and does lower the catalytic activity of the reconstituted complex. The presence of NADH protects against trypsin or Lys-C cleavage, and leads to broadening, and in some cases, shifting, of NMR spectral signals associated with amino acid residues in the surface loop. This indicates that the loop becomes less mobile after nucleotide binding. Observation by NMR during a titration of Th, with NAD' provides evidence of a two-step nucleotide binding reaction. By introducing an appropriate stop codon into the gene coding for the polypeptide of E. coli transhydrogenase cloned into an expression vector, we have prepared the NAD(H)-binding domain equivalent to Th,. The E. coli protein is sensitive to proteolysis by either trypsin or Lys-C in the mobile loop. Judging by the effect of NADH on its NMR spectrum and on the fluorescence of its Trp residues, the protein is capable of binding the nucleotide though it is unable to dock with the membrane-located subunits of transhydrogenase from R. rubrum.

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“…The release of 'mature-like' forms from some lipoprotein precursors in lgt or lsp deletion mutants has been termed 'shaving', whereas the release of either lipoprotein precursors or mature, lipidated lipoproteins can be considered as 'shedding' [37]. Shaving most likely reflects protein-specific proteolytic cleavage events because N-terminal sequencing of released lipoprotein products, from both mutant and wild-type backgrounds, shows differing cleavage positions with respect to the N-terminal cysteine [2,29,37,38].…”

Section: Reviewmentioning

confidence: 99%

Lipoprotein biogenesis in Gram-positive bacteria: knowing when to hold ‘em, knowing when to fold ‘em

Hutchings

Palmer

Harrington

et al. 2009

Trends in Microbiology

181

219

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Evidence that Protein Antigen b of Mycobacterium Tuberculosis is Involved in Phosphate Metabolism

Cited by 58 publications

References 19 publications

Mycobacterium tuberculosisLprG (Rv1411c): A Novel TLR-2 Ligand That Inhibits Human Macrophage Class II MHC Antigen Processing

Mycobacterium tuberculosisLprG (Rv1411c): A Novel TLR-2 Ligand That Inhibits Human Macrophage Class II MHC Antigen Processing

Conformational Dynamics of a Mobile Loop in the NAD(H)‐Binding Subunit of Proton‐Translocating Transhydrogenases from Rhodospirillum Rubrum and Escherichia Coli

Lipoprotein biogenesis in Gram-positive bacteria: knowing when to hold ‘em, knowing when to fold ‘em

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