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- W1515683804 abstract "Dystroglycan is a receptor for extracellular matrix proteins that plays a crucial role during embryogenesis in addition to adult tissue stabilization. A precursor product of a single gene is post-translationally cleaved to form two different subunits, α and β. The extracellular α-dystroglycan is a membrane-associated, highly glycosylated protein that binds to various extracellular matrix molecules, whereas the transmembrane β-dystroglycan binds, via its cytosolic domain, to dystrophin and many other proteins. α- and β-Dystroglycan interact tightly but noncovalently. We have previously shown that the N-terminal region of β-dystroglycan, β-DG(654–750), binds to the C-terminal region of murine α-dystroglycan independently from glycosylation. Preparing a series of deleted recombinant fragments and using solid-phase binding assays, the C-terminal sequence of α-dystroglycan containing the binding epitope for β-dystroglycan has been defined more precisely. We found that a region of 36 amino acids, from position 550–585, is required for binding the extracellular region, amino acids 654–750 of β-dystroglycan. Recently, a dystroglycan-like gene was identified in Drosophila that showed a moderate degree of conservation with vertebrate dystroglycan (31% identity, 48% similarity). Surprisingly, the Drosophila sequence contains a region showing a higher degree of identity and conservation (45% and 66%) that coincides with the 550–585 sequence of vertebrate α-dystroglycan. We have expressed this Drosophila dystroglycan fragment and measured its binding to the extracellular region of vertebrate (murine) β-dystroglycan (Kd = 6 ± 1 µm). These data confirm the proper identification of the β-dystroglycan binding epitope and stress the importance of this region during evolution. This finding might help the rational design of dystroglycan-specific binding drugs, that could have important biomedical applications." @default.
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- W1515683804 date "2001-08-15" @default.
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- W1515683804 title "Identification of the β-dystroglycan binding epitope within the C-terminal region of α-dystroglycan" @default.
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- W1515683804 doi "https://doi.org/10.1046/j.1432-1327.2001.02386.x" @default.
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