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Elastin, a novel extracellular matrix protein adhering to mycobacterial antigen 85 complex.

ABSTRACT: The antigen 85 complex (Ag85) consists of three predominantly secreted proteins (Ag85A, Ag85B, and Ag85C), which play a key role in the mycobacterial pathogenesis and also possess enzymatic mycolyltransferase activity involved in cell wall synthesis. Ag85 is not only considered to be a virulence factor because its expression is essential for intracellular survival within macrophages, but also because it contributes to adherence, invasion, and dissemination of mycobacteria in host cells. In this study, we report that the extracellular matrix components, elastin and its precursor (tropoelastin) derived from human aorta, lung, and skin, serve as binding partners of Ag85 from Mycobacterium tuberculosis. The binding affinity of M. tuberculosis Ag85 to human tropoelastin was characterized (K(D) = 0.13 ± 0.006 ?m), and a novel Ag85-binding motif, AAAKAA(K/Q)(Y/F), on multiple tropoelastin modules was identified. In addition, the negatively charged Glu-258 of Ag85 was demonstrated to participate in an electrostatic interaction with human tropoelastin. Moreover, binding of Ag85 on elastin siRNA-transfected Caco-2 cells was significantly reduced (34.3%), implying that elastin acts as an important ligand contributing to mycobacterial invasion.

SUBMITTER: Kuo CJ

PROVIDER: S-EPMC3567642 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Elastin, a novel extracellular matrix protein adhering to mycobacterial antigen 85 complex.

Kuo Chih-Jung CJ Ptak Christopher P CP Hsieh Ching-Lin CL Hsieh Ching-Lin CL Akey Bruce L BL Chang Yung-Fu YF

The Journal of biological chemistry 20121217 6

The antigen 85 complex (Ag85) consists of three predominantly secreted proteins (Ag85A, Ag85B, and Ag85C), which play a key role in the mycobacterial pathogenesis and also possess enzymatic mycolyltransferase activity involved in cell wall synthesis. Ag85 is not only considered to be a virulence factor because its expression is essential for intracellular survival within macrophages, but also because it contributes to adherence, invasion, and dissemination of mycobacteria in host cells. In this ...[more]

PMID: 23250738

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Elastin, a novel extracellular matrix protein adhering to mycobacterial antigen 85 complex.

Publications

Elastin, a novel extracellular matrix protein adhering to mycobacterial antigen 85 complex.

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