蛋白质二硫键异构酶与α-突触核蛋白的相互作用及对其聚集的影响
Inhibition of α-Synuclein Aggregation by the Interaction Between Protein Disulfide Isomerase and α-Synuclein
蛋白质二硫键异构酶与α-突触核蛋白的相互作用及对其聚集的影响 |
| 裴云山,张偲,刘晓黎,成凯,张则婷,李从刚 |
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Inhibition of α-Synuclein Aggregation by the Interaction Between Protein Disulfide Isomerase and α-Synuclein |
| Yun-shan PEI,Cai ZHANG,Xiao-li LIU,Kai CHENG,Ze-ting ZHANG,Cong-gang LI |
| 图3 PDI b'xa'与αsyn N端相互作用的NMR检测. PDI b'xa'（红色）加入（蓝色）αsyn 1-19多肽(a)、αsyn 30-42多肽(d)、αsyn 1-60蛋白(g)的1H-15N TROSY谱图，选取E239残基展示PDI b'xa'加入各底物后全局残基化学位移变化；PDI b'xa'加入αsyn 1-19多肽(b)、αsyn 30-42多肽(e)、αsyn 1-60 (h)后的CSPs柱状图，以及根据CSPs随底物αsyn 1-19多肽(c)、αsyn 30-42多肽(f)、αsyn 1-60 (i)浓度变化拟合计算解离常数. 柱状图中用CSPs的（平均值+标准差）作为阈值，高于阈值的残基标注在二维谱中，并在b'xa'的晶体结构表面用红色标记；上述高于阈值的残基通过全局拟合得到相应解离常数，离散的扰动残基通过以（平均值+2×标准差）为阈值验证并去除 |
| Fig.3 NMR results showing the interaction between PDI b'xa' with the N-terminal domain of αsyn. Overlaid 1H-15N TROSY spectra of PDI b'xa' (red) with (blue) αsyn 1-19 (a), αsyn 30-42 (d) or αsyn 1-60 (g). E239 were selected as representative residues for global chemical shift perturbations (CSPs) during NMR titration. Residue-resolved CSPs of PDI b'xa' during titrations with αsyn 1-19(b), 30-42(e) and 1-60 (h). KD values were fitted from curves of residues with significant CSPs, as a function of αsyn 1-19(c), αsyn 30-42(f), and αsyn 1-60 (i) concentration. Residues showing significant CSPs were marked in spectra and mapped red on the crystal structure surface of PDI b'xa'. Threshold level was indicated as 'mean+standard deviation'. Disperse residues were verified and removed by the threshold of 'mean +2×standard deviation' |
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