Mammalian alpha 1- and beta 1-syntrophin bind to the alternative splice-prone region of the dystrophin COOH terminus.

• DOI: 10.1083/jcb.128.3.373
• Publication Date: 2004-05-15T01:23:47Z
• Authors: A Suzuki; M Yoshida; E Ozawa
• Keywords: Mammals; 0303 health sciences; Binding Sites; Calcium-Binding Proteins; Molecular Sequence Data; Membrane Proteins; Muscle Proteins; Exons; Dystrophin; Alternative Splicing; 03 medical and health sciences; Dystrophin-Associated Proteins; Animals; Amino Acid Sequence; Protein Binding

The carboxy-terminal region of dystrophin has been suggested to be crucially important for its function prevent muscle degeneration. We have previously shown that this is the locus interacts with sarcolemmal glycoprotein complex, which mediates membrane anchoring dystrophin, as well cytoplasmic peripheral protein, A0 and beta 1-syntrophin (Suzuki, A., M. Yoshida, K. Hayashi, Y. Mizuno, Hagiwara, E. Ozawa. 1994. Eur. J. Biochem. 220:283-292). In work, by using overlay assay technique developed previously, we further analyzed dystrophin-syntrophin/A0 interaction. Two forms mammalian syntrophin, alpha 1- 1-syntrophin, were found bind very close but discrete regions on molecule. Their binding sites are located at vicinity glycoprotein-binding site, correspond amino acid residues encoded exons 73-74 alternatively spliced out in some isoforms. This suggests syntrophin tightly linked functional diversity among Pathologically, it site predominantly expressed skeletal muscle, coincides whose deletion was result a severe phenotype. addition, A0, minor component dystrophin-associated proteins molecular mass 94 kD immunochemically related binds same 1-syntrophin. Finally, based our accumulated evidence, propose revised model domain organization from view point protein-protein interactions.