Structural characterization and binding properties of the hemopexin-like domain of the matrixmetalloproteinase-19 |
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Authors: | Mysliwy Justyna Dingley Andrew J Sedlacek Radislav Grötzinger Joachim |
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Affiliation: | Biochemisches Institut der Christian-Albrechts-Universit?t Kiel, Olshausenstr. 40 24118 Kiel, Germany. |
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Abstract: | The matrixmetalloproteinase-19 (MMP-19) belongs to the superfamily of the zinc-dependent endopeptidases, which are secreted by cells and are involved in the remodeling of the extracellular matrix. The full-length protein consists of a signal peptide, a propeptide, a catalytic domain and a C-terminal hemopexin-like domain. For other members of this superfamily, the hemopexin-like domain has been described to be involved in substrate recognition. In this study, the hemoxpexin domain of MMP-19 was expressed in Escherichia coli, refolded, and purified. For structural characterization, circular dichroism and NMR spectroscopy were used. We show that the hemopexin-like domain of MMP-19 is able to bind calcium and this binding induces a conformational change and an increase in the thermal stability of the domain. MMP-19 promotes proliferation of keratinocytes by cleaving the insulin-like-growth factor binding protein-3, thereby causing the release of IGF-1, which is a potent growth factor for these cells. By plasmon resonance experiments, we show that the isolated hemopexin-like domain is able to bind to the insulin-like-growth factor binding protein-3. These results provide a basis for further structural investigations that could be used for the rational design of potential agonists and antagonists. |
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Keywords: | Matrixmetalloproteinase-19 Hemopexin domain NMR Expression Refolding IGFBP-3 |
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