INTERACTIONS BETWEEN DYSTROPHIN-GLYCOPROTEIN COMPLEX PROTEINS

The organization of the dystrophin glycoprotein complex (DGC) was stud ied by investigating interactions between its components. For this pur pose, mouse dystrophin and syntrophin-1 (alpha-syntrophin) sequences w ere expressed as chimeric fusion proteins and used in overlay binding experiments to probe gel blots of purified rabbit muscle DGC. In order to identify the DGC proteins that bind to different regions of dystro phin, the amino-terminal 385 amino acids, the unique carboxy-terminal domain (amino acids 3266-3678), and the adjacent cysteine-rich region of dystrophin homologous to alpha-actinin (amino acids 3074-3265) were expressed as separate fusion proteins. The cysteine-rich sequences of dystrophin predominantly bound adhalin (gp50) and to full length dyst rophin suggesting that these sequences may also be important to dystro phin dimerization. The carboxy-terminal domain sequences strongly boun d all of the DGC syntrophins and weakly, adhalin, while the amino-term inal sequences of dystrophin bound none of the proteins of this comple x. Fusion proteins containing alpha-syntrophin sequences bound not onl y to dystrophin but also to all three DGC syntrophins, adhalin, and gp 35. The interactions identified here were used to refine the existing model of DGC organization to make it consistent with the current data.