The Unfolding Story of the Chaperonins

Coates, Anthony R. M.; Henderson, Brian E.; Mascagni, Paolo

doi:10.1080/02648725.1999.10647985

Cited by 7 publications

(4 citation statements)

References 72 publications

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“…Exactly how M. tuberculosis evades the machinations of the lysososomal apparatus is not clear. One class of mycobacterial protein that has recently been shown to modulate myeloid cell behavior are the chaperonins, a specific class of molecular chaperone consisting of the oligomeric proteins, Cpn60 and Cpn10 (8,27,29,32). It may be this ability to interact with myeloid cells that accounts for the immunogenicity of the mycobacterial chaperonins.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosisChaperonin 10 Is Secreted in the Macrophage Phagosome: Is Secretion Due to Dissociation and Adoption of a Partially Helical Structure at the Membrane?

et al. 2003

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To confirm that Mycobacterium tuberculosis chaperonin 10 (Cpn10) is secreted outside the live bacillus, infected macrophages were examined by electron microscopy. This revealed that the mycobacterial protein accumulates both in the wall of the bacterium and in the matrix of the phagosomes in which ingested mycobacteria survive within infected macrophages. To understand the structural implications underlying this secretion, a structural study of M. tuberculosis Cpn10 was performed under conditions that are generally believed to mimic the membrane environment. It was found that in buffer-organic solvent mixtures, the mycobacterial protein forms two main species, namely, a partially helical monomer that prevails in dilute solutions at room temperature and a dimer that folds into a ␤-sheet-dominated structure and prevails in either concentrated protein solutions at room temperature or in dilute solutions at low temperature. A partially helical monomer was also found and was completely associated with negatively charged detergents in a micelle-bound state. Remarkably, zwitterionic lipids had no effect on the protein structure. By using N-and C-truncated forms of the protein, the C-and N-terminal sequences were identified as possessing an amphiphilic helical character and as selectively associating with acidic detergent micelles. When the study was extended to other chaperonins, it was found that human Cpn10 is also monomeric and partially helical in dilute organic solvent-buffer mixtures. In contrast, Escherichia coli Cpn10 is mostly dimeric and predominately ␤-sheet in both dilute and concentrated solutions. Interestingly, human Cpn10 also crosses biological membranes, whereas the E. coli homologue is strictly cytosolic. These results suggest that dissociation to partially helical monomers and interaction with acidic lipids may be two important steps in the mechanism of secretion of M. tuberculosis Cpn10 to the external environment.

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Section: Discussionmentioning

confidence: 99%

Mycobacterium tuberculosisChaperonin 10 Is Secreted in the Macrophage Phagosome: Is Secretion Due to Dissociation and Adoption of a Partially Helical Structure at the Membrane?

et al. 2003

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“…The increasing development of antibiotic resistance by the causative organism, M. tuberculosis, argues for identifying ways of blocking the inflammation it produces. One of the constituents that may contribute significantly to such inflammation is chaperonin 60 [17,18]. The level of Cpn60 in bacteria such as M. tuberculosis is approximately 1-2% of the total cell protein and this can rise to 10% or more when bacteria are stressed, as they would be during infection [19,20].…”

Section: Discussionmentioning

confidence: 99%

Highly homologous Mycobacterium tuberculosis chaperonin 60 proteins with differential CD14 dependencies stimulate cytokine production by human monocytes through cooperative activation of p38 and ERK1/2 mitogen-activated protein kinases

Lewthwaite

Clarkin

Coates

et al. 2007

International Immunopharmacology

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“…There is growing evidence that chaperonins have cell-cell signaling actions (reviewed in Coates et al 1999;Ranford et al 2000). However, almost nothing is known about the structure-activity relationship of the cell-stimulating capacity of these proteins.…”

Section: Discussionmentioning

confidence: 99%

Rhizobium leguminosarum chaperonin 60.3, but not chaperonin 60.1, induces cytokine production by human monocytes: activity is dependent on interaction with cell surface CD14

Lewthwaite

George²,

Lund³

et al. 2002

Cell Stress Chaper

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As part of a program of work to understand the interaction of bacterial chaperonins with human leukocytes, we have examined 2 of the 3 chaperonin 60 (Cpn 60) gene products of the nonpathogenic plant symbiotic bacterium, Rhizobium leguminosarum, for their capacity to induce the production of pro-and antiinflammatory cytokines by human cells. Recombinant R. leguminosarum Cpn 60.1 and 60.3 proteins were added to human monocytes at a range of concentrations, and cytokine production was measured by sandwich enzyme-linked immunosorbent assay. In spite of the fact that the 2 R. leguminosarum Cpn 60 proteins share 74.5% amino acid sequence identity, it was found that Cpn 60.3 induced the production of interleukin (IL)-1, tumor necrosis factor alpha, IL-6, IL-8, IL-10, and IL-12, but not IL-4, interferon, or GM-CSF (granulocyte-macrophage colony-stimulating factor), whereas the Cpn 60.1 protein failed to demonstrate any cytokine-inducing activity. The use of neutralizing monoclonal antibodies showed that the cytokine-inducing activity of Cpn 60.3 was dependent on its interaction with CD14. This demonstrates that CD14 mediates not only lipopolysaccharide but also R. leguminosarum Cpn 60.3 cell signaling in human monocytes.

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The Unfolding Story of the Chaperonins

Cited by 7 publications

References 72 publications

Mycobacterium tuberculosisChaperonin 10 Is Secreted in the Macrophage Phagosome: Is Secretion Due to Dissociation and Adoption of a Partially Helical Structure at the Membrane?

Mycobacterium tuberculosisChaperonin 10 Is Secreted in the Macrophage Phagosome: Is Secretion Due to Dissociation and Adoption of a Partially Helical Structure at the Membrane?

Highly homologous Mycobacterium tuberculosis chaperonin 60 proteins with differential CD14 dependencies stimulate cytokine production by human monocytes through cooperative activation of p38 and ERK1/2 mitogen-activated protein kinases

Rhizobium leguminosarum chaperonin 60.3, but not chaperonin 60.1, induces cytokine production by human monocytes: activity is dependent on interaction with cell surface CD14

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