RRC ID 77472
Author Watanabe N, Sasaoka T, Noguchi S, Nishino I, Tanaka T.
Title Cys669-Cys713 disulfide bridge formation is a key to dystroglycan cleavage and subunit association.
Journal Genes Cells
Abstract Dystroglycan (DG) is a widely expressed, transmembrane glycoprotein complex that plays important roles by connecting the extracellular matrix to the cytoskeleton. The alpha- and beta-DG subunits are produced by the cleavage of residues 653 and 654 of the precursor. To clarify the mechanisms involved in cleavage and subunit association, we performed a series of mutation analyses and made the following discoveries: (i) Disruption of the intramolecular disulfide bridge between Cys669 and Cys713 in beta-DG completely abolishes the cleavage, (ii) deletions in the loop region (669-713) and in the C-terminal region of alpha-DG (550-645) abolish the cleavage, (iii) disruption of the disulfide bridge and deletions in the loop region deteriorate the alpha- and beta-DG subunit association, and (iv) at the cleavage site, especially, positions P1' (Ser654) and P6' (Trp659) are critical. Thus, the critical role of the Cys669-Cys713 disulfide bridge formation is, most likely, to form a specific tertiary structure, in which the alpha- and beta-DG domains interact and the cleavage site becomes susceptible to proteolytic reactions. The Cys669 and Cys713 pair is broadly conserved in vertebrates and in some invertebrates, suggesting that the disulfide bridge formation was established early in the evolution of DG.
Volume 12(1)
Pages 75-88
Published 2007-1-1
DOI 10.1111/j.1365-2443.2006.01033.x
PMID 17212656
MeSH Amino Acid Sequence Animals CHO Cells Cells, Cultured Cricetinae Cricetulus Cysteine / chemistry* Cysteine / metabolism Disulfides / chemistry* Dystroglycans / chemistry* Dystroglycans / metabolism* Humans Models, Biological Molecular Sequence Data Protein Subunits / chemistry* Protein Subunits / metabolism* Transfection
IF 1.655
Human and Animal Cells 293(RCB1637)