Dystroglycan (DG) is a membrane-associated protein complex formed by two noncovalently linked subunits, a-DG, a highly glycosylated extracellular protein, and beta-DG, a transmembrane protein. The interface between the two DG subunits, which is crucial to maintain the integrity of the plasma membrane, involves the C-terminal domain of a-DG and the N-terminal extracellular domain of beta-DG. It is well known that under both, physiological and pathological conditions, gelatinases (i.e. MMP-9 and/or MMP-2) can degrade DG, disrupting the connection between the extracellular matrix and the cytoskeleton. However, the molecular mechanisms and the exact cleavage sites underlying these events are still largely unknown. In a previous study, we have characterized the enzymatic digestion of the murine beta-DG ectodomain by gelatinases, identifying a main cleavage site on the beta-DG ectodomain produced by MMP-9. In this article, we have deepened the pattern of the beta-DG ectodomain digestion by MMP-2 by using a combined approach based on SDS-PAGE, Orbitrap, and HPLC-ESI-IT mass spectrometry. Furthermore, we have characterized the kineticparameters of the digestion of some beta-DG ectodomain mutants by gelatinases.

Sbardella, D., Inzitari, R., Iavarone, F., Gioia, M., Marini, S., Sciandra, F., Castagnola, M., Van Den Steen, P., Opdenakker, G., Giardina, B., Brancaccio, A., Coletta, M., Bozzi, M., Enzymatic processing by MMP-2 and MMP-9 of wild-type and mutated mouse ss-dystroglycan, <<IUBMB LIFE>>, 2012; 64 (12): 988-994. [doi:10.1002/iub.1095] [http://hdl.handle.net/10807/40064]

Enzymatic processing by MMP-2 and MMP-9 of wild-type and mutated mouse ss-dystroglycan

Inzitari, Rosanna;Iavarone, Federica;Castagnola, Massimo;Giardina, Bruno;Brancaccio, Andrea;Bozzi, Manuela
2012

Abstract

Dystroglycan (DG) is a membrane-associated protein complex formed by two noncovalently linked subunits, a-DG, a highly glycosylated extracellular protein, and beta-DG, a transmembrane protein. The interface between the two DG subunits, which is crucial to maintain the integrity of the plasma membrane, involves the C-terminal domain of a-DG and the N-terminal extracellular domain of beta-DG. It is well known that under both, physiological and pathological conditions, gelatinases (i.e. MMP-9 and/or MMP-2) can degrade DG, disrupting the connection between the extracellular matrix and the cytoskeleton. However, the molecular mechanisms and the exact cleavage sites underlying these events are still largely unknown. In a previous study, we have characterized the enzymatic digestion of the murine beta-DG ectodomain by gelatinases, identifying a main cleavage site on the beta-DG ectodomain produced by MMP-9. In this article, we have deepened the pattern of the beta-DG ectodomain digestion by MMP-2 by using a combined approach based on SDS-PAGE, Orbitrap, and HPLC-ESI-IT mass spectrometry. Furthermore, we have characterized the kineticparameters of the digestion of some beta-DG ectodomain mutants by gelatinases.
Inglese
Sbardella, D., Inzitari, R., Iavarone, F., Gioia, M., Marini, S., Sciandra, F., Castagnola, M., Van Den Steen, P., Opdenakker, G., Giardina, B., Brancaccio, A., Coletta, M., Bozzi, M., Enzymatic processing by MMP-2 and MMP-9 of wild-type and mutated mouse ss-dystroglycan, <<IUBMB LIFE>>, 2012; 64 (12): 988-994. [doi:10.1002/iub.1095] [http://hdl.handle.net/10807/40064]
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10807/40064
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