Sadoulet-Puccio H M, Rajala M, Kunkel L M
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12413-8. doi: 10.1073/pnas.94.23.12413.
Dystrobrevin, a dystrophin-related and -associated protein, has been proposed to be important in the formation and maintenance of the neuromuscular junction. Dystrobrevin coprecipitates with both the acetylcholine receptor complex as well as the dystrophin glycoprotein complex. Although the nature of dystrobrevin's association with the dystrophin glycoprotein complex remains unclear, it is known that dystrobrevin binds directly to the syntrophins, a heterologous group of dystrophin-associated proteins. Using the yeast two-hybrid system to identify protein-protein interactions, we present evidence for the heterodimerization of dystrobrevin directly with dystrophin. The C terminus of dystrobrevin binds specifically to the C terminus of dystrophin. We further refined this site of interaction to these proteins' homologous coiled-coil motifs that flank their respective syntrophin-binding sites. We also show that the interaction between the dystrobrevin and dystrophin coiled-coil domains is specific and is not due to a nonspecific coiled-coil domain interaction. From the accumulated evidence of protein-protein interactions presented here and elsewhere, we propose a partially revised model of the organization of the dystrophin-associated glycoprotein complex.
肌萎缩蛋白结合蛋白，一种与肌营养不良蛋白相关且相关联的蛋白质，被认为在神经肌肉接头的形成和维持中起重要作用。肌萎缩蛋白结合蛋白与乙酰胆碱受体复合物以及肌营养不良蛋白糖蛋白复合物共沉淀。尽管肌萎缩蛋白结合蛋白与肌营养不良蛋白糖蛋白复合物结合的性质尚不清楚，但已知肌萎缩蛋白结合蛋白直接与肌萎缩蛋白相关蛋白的异源组——突触融合蛋白结合。利用酵母双杂交系统来鉴定蛋白质-蛋白质相互作用，我们提供了肌萎缩蛋白结合蛋白直接与肌营养不良蛋白异源二聚化的证据。肌萎缩蛋白结合蛋白的C末端特异性地结合肌营养不良蛋白的C末端。我们进一步将这种相互作用位点细化到这些蛋白质位于各自突触融合蛋白结合位点两侧的同源卷曲螺旋基序。我们还表明，肌萎缩蛋白结合蛋白和肌营养不良蛋白卷曲螺旋结构域之间的相互作用是特异性的，并非由于非特异性的卷曲螺旋结构域相互作用。根据此处及其他地方积累的蛋白质-蛋白质相互作用的证据，我们提出了一个经部分修订的肌营养不良蛋白相关糖蛋白复合物组织模型。
