The in vivo and in vitro aggregation properties of globular proteins correlate with their conformational stability:: The SH3 case
The in vivo and in vitro aggregation properties of globular proteins correlate with their conformational stability:: The SH3 case
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DOI：
10.1016/j.jmb.2008.03.020
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发表时间：
2008-05-16
影响因子：
5.6
通讯作者：
Ventura, Salvador
中科院分区：
文献类型：
--
作者：
Espargaro, Alba;Castillo, Virginia;Ventura, Salvador
蛋白质错误折叠和沉积是越来越多的使人衰弱的疾病的基础，并构成生物技术中主要关注的问题。在过去的几年中，在体外研究提供了宝贵的见解的物理化学原理蛋白质聚集。然而，有关细胞内蛋白质沉积的决定因素的信息是稀缺的，只有少数系统的研究比较体外和体内的数据已被报道。在这里，我们使用α-血影蛋白的SH 3结构域作为模型球状蛋白，试图了解蛋白质聚集在试管中和在更复杂的细胞环境之间的关系。聚集在大肠杆菌的这个域和一大组突变体的调查，连同它们的顺序和构象特性的分析，使我们能够评估不同的多肽因子的球状蛋白的细胞沉积的贡献。这里提出的数据表明，在体外蛋白质聚集的规则，在体内环境中也是有效的。他们还提供了相关的见解，细胞内蛋白质沉积在构象疾病和重组蛋白生产。(C)2008爱思唯尔有限公司保留所有权利。
Protein misfolding and deposition underlie an increasing number of debilitating human disorders and constitute a problem of major concern in biotechnology. In the last years, in vitro studies have provided valuable insights into the physicochemical principles underlying protein aggregation. Nevertheless, information about the determinants of protein deposition within the cell is scarce and only a few systematic studies comparing in vitro and in vivo data have been reported. Here, we have used the SH3 domain of alpha-spectrin as a model globular protein in an attempt to understand the relationship between protein aggregation in the test-tube and in the more complex cellular environment. The investigation of the aggregation in Escherichia coli of this domain and a large set of mutants, together with the analysis of their sequential and conformational properties allowed us to evaluate the contribution of different polypeptidic factors to the cellular deposition of globular proteins. The data presented here suggest that the rules that govern in vitro protein aggregation are also valid in in vivo contexts. They also provide relevant insights into intracellular protein deposition in both conformational diseases and recombinant protein production. (C) 2008 Elsevier Ltd. All rights reserved.