Enzymatic processing of beta-dystroglycan recombinant ectodomain by MMP-9: identification of the main cleavage site.

IUBMB Life
Manuela BozziMassimo Coletta

Abstract

Dystroglycan (DG) is a membrane receptor belonging to the complex of glycoproteins associated to dystrophin. DG is formed by two subunits, alpha-DG, a highly glycosylated extracellular matrix protein, and beta-DG, a transmembrane protein. The two DG subunits interact through the C-terminal domain of alpha-DG and the N-terminal extracellular domain of beta-DG in a noncovalent way. Such interaction is crucial to maintain the integrity of the plasma membrane. In some pathological conditions, the interaction between the two DG subunits may be disrupted by the proteolytic activity of gelatinases (i.e. MMP-9 and/or MMP-2) that removes a portion or the whole beta-DG ectodomain producing a 30 kDa truncated form of beta-DG. However, the molecular mechanism underlying this event is still unknown. In this study, we carried out proteolysis of the recombinant extracellular domain of beta-DG, beta-DG(654-750) with human MMP-9, characterizing the catalytic parameters of its cleavage. Furthermore, using a combined approach based on SDS-PAGE, MALDI-TOF and HPLC-ESI-IT mass spectrometry, we were able to identify one main MMP-9 cleavage site that is localized between the amino acids His-715 and Leu-716 of beta-DG, and we analysed the proteolytic ...Continue Reading

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Citations

Aug 24, 2013·International Journal of Oncology·Vassilis AggelisRosamonde E Banks
Dec 9, 2014·Matrix Biology : Journal of the International Society for Matrix Biology·Diego SbardellaManuela Bozzi
Nov 22, 2011·Molecular Aspects of Medicine·Diego SbardellaMassimo Coletta
Feb 24, 2015·Matrix Biology : Journal of the International Society for Matrix Biology·Manuela BozziAndrea Brancaccio
Mar 19, 2016·Journal of Cellular Biochemistry·Daniel LeocadioSteve J Winder
Dec 3, 2014·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Grazia R TundoStefano Marini
Apr 1, 2017·BMC Bioinformatics·Wei-Sheng TienKun-Pin Wu
Aug 10, 2019·International Journal of Molecular Sciences·Daniel YoungAntoine Dufour

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