Mammalian alpha 1- and beta 1-syntrophin bind to the alternative splice-prone region of the dystrophin COOH terminus.
Mammalian alpha 1- and beta 1-syntrophin bind to the alternative splice-prone region of the dystrophin COOH terminus.
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DOI：
10.1083/jcb.128.3.373
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发表时间：
1995-02
期刊：
影响因子：
--
通讯作者：
Ozawa E
中科院分区：
文献类型：
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作者：
Suzuki A;Yoshida M;Ozawa E
肌营养不良蛋白的羧基末端区域被认为对其防止肌肉变性的功能至关重要。我们之前已经表明，该区域是与肌层糖蛋白复合物相互作用的位点，该复合物介导肌营养不良蛋白的膜锚定，以及与细胞质外周膜蛋白A0和β 1-syntrophin相互作用（Suzuki， A.， M. Yoshida， K. Hayashi， Y. Mizuno， Y. Hagiwara和E. Ozawa. 1994）。欧元。[j] .生物化学学报，2008,32(2):387 - 398。在这项工作中，我们使用先前开发的覆盖分析技术，进一步分析了肌营养不良蛋白-syntrophin/A0相互作用。两种形式的哺乳动物syntrophin， α - 1-和β - 1- syntrophin，被发现与肌营养不良蛋白分子上非常接近但离散的区域结合。它们的结合位点位于糖蛋白结合位点附近，与外显子73-74编码的氨基酸残基相对应，这些氨基酸残基在某些同工型中被选择性剪接。这表明syntrophin的功能与肌营养不良蛋白同种异构体的功能多样性密切相关。在病理学上，重要的是α 1- syntrophin的结合位点，主要在骨骼肌中表达，与被认为缺失导致严重表型的区域一致。此外，A0是抗营养不良蛋白相关蛋白的一个小成分，分子量为94 kD，免疫化学上与syntrophin相关，与β 1-syntrophin结合在同一位点。最后，基于我们积累的证据，我们从蛋白质-蛋白质相互作用的角度提出了一个修正的肌营养不良蛋白结构域组织模型。
The carboxy-terminal region of dystrophin has been suggested to be crucially important for its function to prevent muscle degeneration. We have previously shown that this region is the locus that interacts with the sarcolemmal glycoprotein complex, which mediates membrane anchoring of dystrophin, as well as with the cytoplasmic peripheral membrane protein, A0 and beta 1-syntrophin (Suzuki, A., M. Yoshida, K. Hayashi, Y. Mizuno, Y. Hagiwara, and E. Ozawa. 1994. Eur. J. Biochem. 220:283- 292). In this work, by using the overlay assay technique developed previously, we further analyzed the dystrophin-syntrophin/A0 interaction. Two forms of mammalian syntrophin, alpha 1- and beta 1- syntrophin, were found to bind to very close but discrete regions on the dystrophin molecule. Their binding sites are located at the vicinity of the glycoprotein-binding site, and correspond to the amino acid residues encoded by exons 73-74 which are alternatively spliced out in some isoforms. This suggests that the function of syntrophin is tightly linked to the functional diversity among dystrophin isoforms. Pathologically, it is important that the binding site for alpha 1- syntrophin, which is predominantly expressed in skeletal muscle, coincides with the region whose deletion was suggested to result in a severe phenotype. In addition, A0, a minor component of dystrophin- associated proteins with a molecular mass of 94 kD which is immunochemically related to syntrophin, binds to the same site as beta 1-syntrophin. Finally, based on our accumulated evidence, we propose a revised model of the domain organization of dystrophin from the view point of protein-protein interactions.