Publikation: Identification of the beta-dystroglycan binding epitope within the C-terminal region of alpha-dystroglycan
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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.
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SCIANDRA, Francesca, Martina SCHNEIDER, Bruno GIARDINA, Stefan BAUMGARTNER, Tamara C. PETRUCCI, Andrea BRANCACCIO, 2001. Identification of the beta-dystroglycan binding epitope within the C-terminal region of alpha-dystroglycan. In: European Journal of Biochemistry. Wiley-Blackwell. 2001, 268(16), pp. 4590-4597. ISSN 0014-2956. Available under: doi: 10.1046/j.1432-1327.2001.02386.xBibTex
@article{Sciandra2001-08Ident-50880, year={2001}, doi={10.1046/j.1432-1327.2001.02386.x}, title={Identification of the beta-dystroglycan binding epitope within the C-terminal region of alpha-dystroglycan}, number={16}, volume={268}, issn={0014-2956}, journal={European Journal of Biochemistry}, pages={4590--4597}, author={Sciandra, Francesca and Schneider, Martina and Giardina, Bruno and Baumgartner, Stefan and Petrucci, Tamara C. and Brancaccio, Andrea} }
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