J proteins direct the processing of misfolded proteins within cellular protein quality control

所有蛋白质都需要 获得它们定义的三维构象， 这个过程被称为蛋白质折叠。蛋白质折叠可能受到挑战 许多环境和基因攻击导致错误折叠的蛋白质 这些细胞通常功能失调，对细胞有毒。细胞蛋白 质量控制，即涉及蛋白质合成的所有机制， 因此，在所有活细胞中， 使细胞免受蛋白质错误折叠的有害后果。分子 J蛋白类分子伴侣是细胞蛋白质质量的关键因素 控制，因为它们有助于适当的蛋白质合成，维持， 降解J蛋白构成了最多样化的分子伴侣， 到目前为止，已分析的所有生物体中不同J蛋白的数量 超过了所有其他分子伴侣的数量。这种令人困惑的多样性 这意味着J蛋白进化为选择性靶向客户蛋白， 在细胞蛋白质质量控制中执行专门的功能 网络然而，支持这种靶特异性的分子和细胞机制 并且单个J蛋白的不同细胞功能仍不清楚。我们 这里提出的研究计划旨在确定目标特异性， J蛋白的独特细胞作用， 系统生物学、细胞生物学和计算方法， 酿酒酵母）作为遗传上易处理的模式生物。我们的研究将 确定了J蛋白指定蛋白质的一般生物学原理。 活性的细胞蛋白质质量控制，从而执行功能 在活细胞中的不同作用。

All proteins need to acquire their defined three-dimensional conformation in order to function properly, a process termed protein folding. Protein folding can be challenged by numerous environmental and genetic assaults resulting in misfolded proteins that are usually dysfunctional and often toxic to the cell. Cellular protein quality control, i.e. all mechanisms involved in protein synthesis, maintenance, and degradation, has thus evolved in all living cells to protect cells from the detrimental consequences of protein misfolding. Molecular chaperones of the J protein class are key players in cellular protein quality control as they facilitate proper protein synthesis, maintenance, and degradation. J proteins constitute the most diverse class of molecular chaperones as the number of different J proteins in all organism that have been analyzed so far exceeds the number of all other molecular chaperone. This perplexing diversity implies that J proteins evolved to selectively target client proteins and execute specialized functions within the cellular protein quality control network. Yet the molecular and cellular mechanisms underpinning this target specificity and the distinct cellular functions of individual J proteins remain unclear. Our research program proposed here aims to determine the target specificity and distinct cellular roles of J proteins by applying a combination of genetic, systems biology, cell biological and computational approaches using yeast (Saccharomyces cerevisiae) as a genetically tractable model organism. Our research will determine general biological principles by which J proteins specify the activity of cellular protein quality control and thus execute functionally distinct roles in living cells.