Young P, Ehler E, Gautel M
European Molecular Biology Laboratory, Structural Biology Division, 69117 Heidelberg, Germany.
J Cell Biol. 2001 Jul 9;154(1):123-36. doi: 10.1083/jcb.200102110.
Vertebrate-striated muscle is assumed to owe its remarkable order to the molecular ruler functions of the giant modular signaling proteins, titin and nebulin. It was believed that these two proteins represented unique results of protein evolution in vertebrate muscle. In this paper we report the identification of a third giant protein from vertebrate muscle, obscurin, encoded on chromosome 1q42. Obscurin is approximately 800 kD and is expressed specifically in skeletal and cardiac muscle. The complete cDNA sequence of obscurin reveals a modular architecture, consisting of >67 intracellular immunoglobulin (Ig)- or fibronectin-3-like domains with multiple splice variants. A large region of obscurin shows a modular architecture of tandem Ig domains reminiscent of the elastic region of titin. The COOH-terminal region of obscurin interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin. Both proteins coassemble during myofibrillogenesis. During the progression of myofibrillogenesis, all obscurin epitopes become detectable at the M band. The presence of a calmodulin-binding IQ motif, and a Rho guanine nucleotide exchange factor domain in the COOH-terminal region suggest that obscurin is involved in Ca(2+)/calmodulin, as well as G protein-coupled signal transduction in the sarcomere.
脊椎动物的横纹肌被认为其显著的有序性归因于巨大的模块化信号蛋白肌联蛋白和伴肌动蛋白的分子标尺功能。人们曾认为这两种蛋白质代表了脊椎动物肌肉中蛋白质进化的独特结果。在本文中，我们报告了从脊椎动物肌肉中鉴定出的第三种巨大蛋白质—— obscurin，它由1号染色体q42编码。Obscurin 约为800 kD，特异性表达于骨骼肌和心肌。Obscurin 的完整 cDNA 序列揭示了一种模块化结构，由超过67个细胞内免疫球蛋白（Ig）或纤连蛋白3样结构域以及多个剪接变体组成。Obscurin 的一个大区域呈现出串联 Ig结构域的模块化结构，让人联想到肌联蛋白的弹性区域。Obscurin 的COOH末端区域通过两个特定的Ig样结构域与肌联蛋白的NH(2)末端Z盘区域相互作用。在肌原纤维形成过程中，这两种蛋白质共同组装。在肌原纤维形成过程中，所有 obscurin 表位在M带处均可检测到。COOH末端区域存在钙调蛋白结合IQ基序和Rho鸟嘌呤核苷酸交换因子结构域，表明obscurin参与了肌节中的Ca(2+)/钙调蛋白以及G蛋白偶联信号转导。
