Liao R, Wang C K, Cheung H C
Graduate Program in Biophysical Sciences, University of Alabama, Birmingham 35294-2041.
Biophys J. 1992 Oct;63(4):986-95. doi: 10.1016/S0006-3495(92)81685-5.
We have carried out a time-resolved fluorescence study of the single tryptophanyl residue (Trp-192) of bovine cardiac Tnl (CTnl). With excitation at 300 nm, the intensity decay was resolved into three components by a nonlinear least-squares analysis with lifetimes of 0.60, 2.22, and 4.75 ns. The corresponding fractional amplitudes were 0.27, 0.50, and 0.23, respectively. These decay parameters were not sensitive to complexation of CTnl with cardiac troponin C (CTnC), and magnesium and calcium had no significant effect on the decay parameters. After incubation with 3':5'-cyclic AMP-dependent protein kinase, the intensity decay of CTnl required a fourth exponential term for satisfactory fitting with lifetimes of 0.11, 0.81, 1.95, and 6.63 ns and fractional amplitudes of 0.06, 0.37, 0.27, and 0.29, respectively. When bound to CTnC, the intensity decay of phosphorylated CTnl (p-CTnl) also required four exponential terms for satisfactory fitting, but the longest lifetime increased by a factor of 1.7. The decay parameters obtained from the complex formed between p-CTnl and CTnC were not sensitive to either magnesium or calcium. The anisotropy decay was resolved into two components with rotational correlation times of 0.90 and 23.48 ns. Phosphorylation resulted in a decrease of the long correlation time to 14.61 ns. The anisotropy values recovered at zero time suggest that the side chain of the Trp-192 had considerable subnanosecond motional freedom not resolved in these experiments. Within the CTnl.CTnC complex, the unresolved fast motions appeared sensitive to calcium binding to the calcium-specific site of CTnC. The observed emission heterogeneity is discussed in terms of possible excited-state interactions in conjunction with the predicted secondary structure of CTnl. The loss of molecular asymmetry of cardiac troponin I induced by phosphorylation as demonstrated in this work may be related to the known physiological effect of beta-agonists on cardiac contractility.
我们对牛心肌肌钙蛋白I(CTnI)的单个色氨酸残基(Trp-192)进行了时间分辨荧光研究。在300nm激发下,通过非线性最小二乘法分析将强度衰减解析为三个成分,寿命分别为0.60、2.22和4.75ns。相应的分数振幅分别为0.27、0.50和0.23。这些衰减参数对CTnI与心肌肌钙蛋白C(CTnC)的复合不敏感,镁和钙对衰减参数也没有显著影响。用3':5'-环磷酸腺苷依赖性蛋白激酶孵育后,CTnI的强度衰减需要第四个指数项才能满意拟合,寿命分别为0.11、0.81、1.95和6.63ns,分数振幅分别为0.06、0.37、0.27和0.29。当与CTnC结合时,磷酸化的CTnI(p-CTnI)的强度衰减也需要四个指数项才能满意拟合,但最长寿命增加了1.7倍。从p-CTnI和CTnC形成的复合物中获得的衰减参数对镁或钙均不敏感。各向异性衰减解析为两个成分,旋转相关时间分别为0.90和23.48ns。磷酸化导致长相关时间降至14.61ns。零时刻恢复的各向异性值表明,Trp-192的侧链具有相当大的亚纳秒级运动自由度,在这些实验中未得到解析。在CTnI.CTnC复合物中,未解析的快速运动似乎对钙结合到CTnC的钙特异性位点敏感。结合CTnI的预测二级结构,从可能的激发态相互作用角度讨论了观察到的发射异质性。这项工作中证明的磷酸化诱导的心肌肌钙蛋白I分子不对称性的丧失可能与β-激动剂对心肌收缩力的已知生理作用有关。