Dystrobrevin and dystrophin: An interaction through coiled-coil motifs
Dystrobrevin and dystrophin: An interaction through coiled-coil motifs
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DOI：
10.1073/pnas.94.23.12413
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发表时间：
1997-11-11
影响因子：
11.1
通讯作者：
Kunkel, LM
中科院分区：
文献类型：
--
作者：
SadouletPuccio, HM;Rajala, M;Kunkel, LM
Dystrobrevin是一种抗肌萎缩蛋白相关蛋白，已被认为在神经肌肉接头的形成和维持中很重要。短肌养蛋白与乙酰胆碱受体复合物以及肌养蛋白糖蛋白复合物共沉淀。尽管小肌养蛋白与肌营养不良蛋白糖蛋白复合物的关联的性质仍不清楚，但已知小肌养蛋白直接与肌营养不良蛋白相关蛋白质的异源组--突触营养蛋白结合。利用酵母双杂交系统鉴定蛋白质-蛋白质相互作用，我们证明了dystrobrevin与dystrophin直接异二聚化，dystrobrevin的C末端特异性结合dystrophin的C末端。我们进一步完善了这个相互作用的网站，这些蛋白质的同源卷曲螺旋基序，侧翼各自的促突触蛋白结合位点。我们还表明，肌养短蛋白和肌养蛋白卷曲螺旋结构域之间的相互作用是特定的，而不是由于一个非特异性卷曲螺旋结构域的相互作用，从这里和其他地方提出的蛋白质-蛋白质相互作用的积累的证据，我们提出了一个部分修订模型的肌养蛋白相关的糖蛋白复合物的组织。
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.