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首页> 外文期刊>Biochemistry >Modulation of troponin T molecular conformation and flexibility by metal ion binding to the NH2-terminal variable region
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Modulation of troponin T molecular conformation and flexibility by metal ion binding to the NH2-terminal variable region

机译：用金属离子结合与NH2末端可变区的肌钙蛋白T分子构象和柔韧性的调节

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Troponin T (TnT) plays an allosteric signal transduction role in the actin thin-filament-based Ca2+-regulation of striated muscle contraction. Developmentally regulated alternative RNA splicing produces TnT isoforms differing in their NH2-terminal structure. Physical property variations of the NH2-terminal hypervariable region of TnT may have a role in tuning the Ca2+-sensitivity and overall cooperativity of the muscle. We have previously demonstrated that metal ion or monoclonal antibody binding to the NH2-terminal region can modulate the epitopic conformation and troponin I and tropomyosin binding affinity of TnT. To further establish the molecular basis of this conformational and functional modulation, we have characterized the NH2-terminal variable region-originated secondary conformational effect in TnT using fluorescence spectral analysis. The chicken fast skeletal muscle TnT isoform, TnT8e16, containing a cluster of transition-metal ion binding sites (Tx) in the NH2-terminal variable region was used in this study. TnT8e16 was titrated for Cu(II) binding-induced changes in fluorescence intensity and anisotropy of the COOH-domain Trp residues (W234, W236, and W285), which demonstrated considerable environmental sensitivity in TnT denaturation studies, Nonlinear Stern-Volmer plots of Trp quenching indicated a metal ion binding-induced conformational change in TnT, Fluorescence anisotropy changes upon metal ion binding indicated a decrease in the mobility of the Trp residues and an increase in the flexibility of fluorescein-labeled Cys263 in the COOH domain. These data support a model that the alternatively spliced NH2-terminal variable region of TnT modulates conformation and flexibility of other domains of the protein. [References: 42]
机译：肌钙蛋白T（TNT）在基于肌动蛋白的薄丝的Ca2 + -regulation的条纹肌肉收缩中起着颠振信号转导作用。发育调节的替代RNA剪接产生在其NH 2末端结构中不同的TNT同种型。 TNT的NH2末端高变区域的物理性质变化可以在调整CA2 + - 敏感度和肌肉的总体合作中具有作用。我们之前已经证明，与NH 2末端区域结合的金属离子或单克隆抗体可以调节表位构象和肌钙蛋白I以及TNT的肌瘤结合亲和力。为了进一步建立这种构象和功能调节的分子基础，我们已经表征了使用荧光光谱分析在TNT中的NH 2末端可变区发起的次级构象效应。本研究使用鸡快速骨骼肌TNT同种型TNT8E16，含有NH 2 - 末端可变区中的过渡金属离子结合位点（TX）的簇。 TNT8E16滴定TNT8E16用于Cu（II）结合诱导的荧光强度和COOH-结构域TRP残基的各向异性的变化（W234，W236和W285），其在TNT变性研究中表现出相当大的环境敏感性，TRP的非线性船尾Volmer曲线淬火表明TNT的金属离子结合诱导的构象变化，金属离子结合时的荧光各向异性变化表明TRP残基的迁移率降低以及荧光素标记的Cys263在COOH结构域中的柔韧性的增加。这些数据支持一种模型，即TNT的交替剪接的NH 2末端可变区调节蛋白质的其他结构域的构象和柔韧性。 [参考：42]

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