Developmentally regulated, alternative RNA splicing-generated pectoral muscle-specific troponin T isoforms and role of the NH2-terminal hypervariable region in the tolerance to acidosis
Developmentally regulated, alternative RNA splicing-generated pectoral muscle-specific troponin T isoforms and role of the NH2-terminal hypervariable region in the tolerance to acidosis
复制标题
DOI：
10.1074/jbc.273.43.27858
复制
发表时间：
1998-10-23
影响因子：
4.8
通讯作者：
Jin, JP
中科院分区：
文献类型：
--
作者：
Ogut, O;Jin, JP
肌钙蛋白T（TnT）氨基端可变区（NH 2-terminal variable region of troponin T，NH 2-terminal variable region of TnT）的结构-功能关系对于理解发育或肌肉特异性TnT异构体的生理意义是必不可少的。在鸡快骨骼肌TnT中发现了一个重复的过渡金属结合序列（H（E/A）EAH）（4-7）（Tx），在本研究中，发育调节胸肌特异性表达这种新的TnT亚型的特点。发现可变的氨基末端决定了所表达的TnT同种型的等电点，并且Tx序列的成人肌肉特异性包含导致胸肌TnT，其在其NH 2-末端区段中比腓肠肌TnT显著更酸性，测试pH对TnT与肌钙蛋白I和原肌球蛋白相互作用的影响的实验表明，尽管酸性TnT亚型与肌钙蛋白I的相互作用与碱性TnT同工型相比，酸性TnT同工型对pH降低的敏感性较低，酸性TnT同工型与原肌球蛋白的结合亲和力受pH降低的影响最小。鉴于大多数成人骨骼肌表达碱性快TnT同工型，酸性和碱性TnT同工型之间的转换可能在肌肉对酸中毒的功能适应中发挥作用。
The structure-function relationship of the alternative RNA splicing-generated NH2-terminal variable region of troponin T (TnT) is essential for understanding the physiological significance of developmental or muscle-specific TnT isoforms, Representing the hypervariable nature of the NH2-terminal region, a repeating transition metal-binding sequence (H(E/A)EAH)(4-7) (Tx) has been found in chicken fast skeletal muscle TnT, In the present study, the developmentally regulated pectoral muscle-specific expression of this novel TnT isoform has been characterized. It was found that the variable amino terminus determined the isoelectric points of the TnT isoforms expressed, and the adult muscle-specific inclusion of the Tx sequence resulted in pectoralis TnTs, which were significantly more acidic in their NH2-terminal segment versus gastrocnemius TnTs, Experiments testing the effect of pH on TnT interaction with troponin I and tropomyosin indicated that although the interaction of acidic TnT isoforms with troponin I was less sensitive to the decrease of pH than the basic TnTs, the binding affinity of acidic TnT isoforms with tropomyosin was minimally affected by the decreased pH in contrast to basic TnT isoforms, Given that the majority of adult skeletal muscles express basic fast TnT isoforms, the switching between acidic and basic TnT isoforms may play a role in the functional adaptation of muscle to acidosis.