Kinetic model of BiP- and PDI-mediated protein folding and assembly
Kinetic model of BiP- and PDI-mediated protein folding and assembly
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DOI：
10.1006/jtbi.2001.2478
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发表时间：
2002-02-21
影响因子：
2
通讯作者：
Asenjo, JA
中科院分区：
文献类型：
--
作者：
González, R;Andrews, BA;Asenjo, JA
重链结合蛋白（BiP）和蛋白质二硫键异构酶（PDI）介导的蛋白质折叠和组装的机制已被提出。它考虑了BiP伴侣作用和PDI催化活性。已开发的动力学模型的基础上提出的机制。该模型用于量化多肽浓度和比率的影响，以及BiP和PDI浓度对折叠和组装动力学的影响。发现了使组装时间最小化的多肽浓度的最佳值，并且确定了高于或低于最佳值的多肽浓度的不同动力学行为。脉冲追逐实验和组装时间对未组装的多肽比例的依赖性模型预测的是在体外和体内的抗体和人绒毛膜促性腺激素（hCG），以及牛胰蛋白酶抑制剂（BPTI）的折叠和组装过程中发现的那些类似。该模型还解释了BiP和PDI过表达期间折叠和组装速率的增加。
A mechanism for heavy chain binding protein (BiP)- and protein disulfide isomerase (PDI)mediated protein folding and assembly has been proposed. It considers BiP chaperoning action and PDI catalytic activity. A kinetic model has been developed based on the proposed mechanism. The model was used for quantifying the influence of polypeptide concentration and ratio, and the effect of BiP and PDI concentration on the kinetics of folding and assembly. An optimum value for polypeptide concentration that minimizes assembly times was found, and different kinetic behaviors were identified for polypeptide concentrations higher or lower than the optimum. Pulse-chase experiments and the dependence of assembly time on unassembled polypeptides ratio predicted by the model are similar to those found during in vitro and in vivo folding and assembly of antibodies and human chorionic gonadotropin (hCG), as well as bovine pancreatic trypsin inhibitor (BPTI) folding. The model also explains the increase in folding-and assembly rates during overexpression of BiP and PDI.