Structure of a WW domain containing fragment of dystrophin in complex with β-dystroglycan
Structure of a WW domain containing fragment of dystrophin in complex with β-dystroglycan
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DOI：
10.1038/77923
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发表时间：
2000-08-01
期刊：
影响因子：
--
通讯作者：
Eck, MJ
中科院分区：
文献类型：
--
作者：
Huang, X;Poy, F;Eck, MJ
肌营养不良蛋白和β-肌营养不良蛋白聚糖是肌营养不良蛋白-糖蛋白复合物（DGC）的组分，DGC是跨越细胞膜并将肌动蛋白细胞骨架连接到细胞外基底层的多分子组装体。肌营养不良蛋白基因的缺陷是杜氏肌营养不良症和啄木鸟肌营养不良症的原因。肌营养不良蛋白的C-末端区域结合β-肌营养不良聚糖的胞质尾部，部分地通过其WW结构域与β-肌营养不良聚糖尾部中富含脯氨酸的蛾的相互作用。在这里，我们报告的晶体结构，这部分的肌营养不良蛋白在复杂的脯氨酸丰富的结合位点β-肌营养不良蛋白聚糖。结构表明，肌营养不良蛋白WW域嵌入在相邻的螺旋区域，其中包含两个EF-手状结构域。β-肌营养不良蛋白聚糖肽结合由WW结构域和这些EF-手之一形成的复合表面。此外，该结构揭示了WW结构域和SH 3结构域所采用的脯氨酸识别机制的惊人相似之处。
Dystrophin and beta-dystroglycan are components of the dystrophin-glcoprotein complex (DGC), a multimolecular assembly that spans the cell membrane and links the actin cytoskeleton to the extracellular basal lamina. Defects in the dystrophin gene are the cause of Duchenne and pecker muscular dystrophies. The C-terminal region of dystrophin binds the cytoplasmic tail of beta-dystroglycan, in part through the interaction of its WW domain with a proline-rich moth in the tail of beta-dystroglycan. Here we report the crystal structure of this portion of dystrophin in complex with the proline-rich binding site in beta-dystroglycan. The structure shows that the dystrophin WW domain is embedded in an adjacent helical region that contains two EF-hand-like domains. The beta-dystroglycan peptide binds a composite surface formed by the WW domain and one of these EF-hands. Additionally, the structure reveals striking similarities in the mechanisms of proline recognition employed by WW domains and SH3 domains.