The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system.
The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system.
复制标题
DOI：
--
复制
发表时间：
2001
影响因子：
20.1
通讯作者：
M. Bang;T. Centner;F. Fornoff;A. J. Geach;M. Gotthardt;M. Mcnabb;C. Witt;D. Labeit;C. Gregorio;H. Granzier;S. Labeit
中科院分区：
文献类型：
--
作者：
M. Bang;T. Centner;F. Fornoff;A. J. Geach;M. Gotthardt;M. Mcnabb;C. Witt;D. Labeit;C. Gregorio;H. Granzier;S. Labeit
Titin是一种巨大的脊椎动物横纹肌蛋白，对肌原纤维的弹性和结构完整性至关重要。我们发现人类titin基因的完整序列包含363个外显子，共编码38138个残基（4200 kDa）。在其中心i带区，发现了47个新的PEVK外显子，这有助于titin的可扩展弹簧特性。此外，还鉴定出3个独特的I-band titin外显子（命名为novex-1至-3）。novx -3作为一种替代的titin c -末端。novx -3 titin亚型的大小约为700 kDa，从Z1-Z2 （titin的n端）到novx -3 （c端外显子）。novox -3 titin与obscurin特异性相互作用，后者是一种721 kda的肌纤维蛋白，由57个Ig/FN3结构域组成，随后在其c端有一个IQ、SH3、DH和PH结构域。当在活心肌细胞中以GFP融合蛋白的形式表达时，obscurin结构域Ig48/Ig49与novex-3 titin结合并靶向z线区域。免疫电镜检测到靠近z线边缘的c端Ig48/Ig49 obscurin表位。距z线的距离随肌节长度的变化而变化，表明novex-3 titin/obscurin复合物形成了一个弹性Z-disc - I-band连接系统。该系统可以将靠近z盘的钙依赖性、SH3-和gtpase调节的信号通路连接在一起，z盘是一种与心肌病期间肌节重组越来越相关的结构。
Titin is a giant vertebrate striated muscle protein with critical importance for myofibril elasticity and structural integrity. We show here that the complete sequence of the human titin gene contains 363 exons, which together code for 38 138 residues (4200 kDa). In its central I-band region, 47 novel PEVK exons were found, which contribute to titin's extensible spring properties. Additionally, 3 unique I-band titin exons were identified (named novex-1 to -3). Novex-3 functions as an alternative titin C-terminus. The novex-3 titin isoform is approximately 700 kDa in size and spans from Z1-Z2 (titin's N-terminus) to novex-3 (C-terminal exon). Novex-3 titin specifically interacts with obscurin, a 721-kDa myofibrillar protein composed of 57 Ig/FN3 domains, followed by one IQ, SH3, DH, and a PH domain at its C-terminus. The obscurin domains Ig48/Ig49 bind to novex-3 titin and target to the Z-line region when expressed as a GFP fusion protein in live cardiac myocytes. Immunoelectron microscopy detected the C-terminal Ig48/Ig49 obscurin epitope near the Z-line edge. The distance from the Z-line varied with sarcomere length, suggesting that the novex-3 titin/obscurin complex forms an elastic Z-disc to I-band linking system. This system could link together calcium-dependent, SH3-, and GTPase-regulated signaling pathways in close proximity to the Z-disc, a structure increasingly implicated in the restructuring of sarcomeres during cardiomyopathies.