Department of Biology, National University of Ireland, Maynooth, Co. Kildare, Ireland.
Curr Protein Pept Sci. 2013 Dec;14(8):680-97. doi: 10.2174/13892037113146660083.
The largest human gene is represented by the X-chromosomal dystrophin gene of 2.4 million bases, which encodes for the membrane cytoskeletal protein dystrophin. The dystrophin isoform Dp427 has a subsarcolemmal location and forms a supramolecular membrane assembly with a variety of glycoproteins. In healthy muscle fibres, dystrophin acts as an actin-binding protein that links the cytoskeleton via the α/β-dystroglycan complex to the extracellular matrix protein laminin. This trans-sarcolemmal complex is believed to stabilize the muscle surface and thus prevents membrane rupturing during excitation-contraction-relaxation cycles. In the highly progressive muscle wasting disease Duchenne muscular dystrophy, the primary deficiency in dystrophin causes a drastic reduction in dystrophin-associated glycoproteins, which renders muscle fibres more susceptible to necrosis. Following the biochemical and cell biological characterization of the dystrophin-glycoprotein complex, several mass spectrometry-based proteomic studies have investigated global changes in dystrophin-deficient muscle tissues. This review briefly outlines the basic domain structure of Dp427 and the composition of the dystrophin-associated glycoprotein complex from skeletal muscle. A detailed discussion of recent proteomic analyses of the purified dystrophin-glycoprotein complex is included, as well as a summary of mass spectrometric surveys of dystrophic specimens. The study of these new areas of muscle proteomics tends to improve our understanding of the normal function of dystrophin in contractile fibres and better define the molecular mechanism of X-linked muscular dystrophy.
人类最大的基因是由 240 万个碱基对组成的 X 染色体肌营养不良蛋白基因，它编码膜细胞骨架蛋白肌营养不良蛋白。肌营养不良蛋白同工型 Dp427 位于肌小节下，与多种糖蛋白一起形成超分子膜组装。在健康的肌肉纤维中，肌营养不良蛋白作为一种肌动蛋白结合蛋白，通过α/β-肌营养不良蛋白聚糖复合物将细胞骨架与细胞外基质蛋白层粘连蛋白连接起来。这个跨肌小节的复合物被认为可以稳定肌肉表面，从而防止在兴奋-收缩-松弛循环期间膜破裂。在进展迅速的肌肉消耗性疾病杜氏肌营养不良症中，肌营养不良蛋白的主要缺乏导致与肌营养不良蛋白相关的糖蛋白急剧减少，使肌肉纤维更容易坏死。在对肌营养不良蛋白-糖蛋白复合物进行生化和细胞生物学特征分析之后，几项基于质谱的蛋白质组学研究已经调查了肌营养不良蛋白缺陷肌肉组织中的全局变化。这篇综述简要概述了 Dp427 的基本结构域和骨骼肌中肌营养不良蛋白相关糖蛋白复合物的组成。详细讨论了最近对纯化的肌营养不良蛋白-糖蛋白复合物的蛋白质组学分析，并对肌营养不良标本的质谱调查进行了总结。这些肌肉蛋白质组学新领域的研究有助于提高我们对肌营养不良蛋白在收缩纤维中的正常功能的理解，并更好地定义 X 连锁肌营养不良症的分子机制。
