Alpha 1-antitrypsin polymerization: a fluorescence correlation spectroscopic study.

Alpha 1-antitrypsin polymerization: a fluorescence correlation spectroscopic study.
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Alpha 1-抗胰蛋白酶聚合:荧光相关光谱研究。

DOI:
10.1021/bi048662e
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发表时间:
2005
期刊:
Biochemistry.
影响因子:
--
通讯作者:
Gai,Feng
Gai,Feng
中科院分区:
--
文献类型:
--
作者:
Purkayastha,Pradipta;Klemke,JasonW;Lavender,Stacey;Oyola,Rolando;Cooperman,BarryS;Gai,Feng

文献摘要

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α1-抗胰蛋白酶 (AT) 是丝氨酸蛋白酶抑制剂家族中循环最丰富的人类蛋白酶抑制剂。 AT 的聚合导致 α1-抗胰蛋白酶缺乏,已通过各种集成方法在体外进行了广泛的研究。在这里,我们报告使用荧光相关光谱来进一步了解这一过程。在 45°C、50°C 和 55°C 下进行的聚合 AT 扩散时间分布的测量清楚地表明存在动力学滞后阶段,在此期间,在形成较长聚合物的异质混合物之前形成了短低聚物,并表明似乎亚稳态的长聚合物是通过较短低聚物的缩合产生的。
α1-Antitrypsin (AT) is the most abundantly circulating human proteinase inhibitor in the serpin family. The polymerization of AT, leading to α1-antitrypsin deficiency, has been studied extensively in vitro by a variety of ensemble methods. Here we report the use of fluorescence correlation spectroscopy to gain further insight into this process. Measurements of the distributions of diffusion times of polymerizing AT, carried out at 45, 50, and 55 °C, clearly show the existence of a kinetic lag phase, during which short oligomers are formed, prior to the formation of heterogeneous mixtures of longer polymers, and suggest that long polymers, which appear to be metastable, are produced through the condensation of shorter oligomers.