MECHANISM OF ACTION OF E COLI PROTEIN EXPORT FACTORS

蛋白质定位是一个至关重要的细胞过程， 蛋白质没有正确定位的疾病综合征的例子 揭示了细胞器故障的深刻生理后果， 生物起源 在大肠杆菌中，secB基因产物参与 蛋白质定位并促进蛋白质输出到细胞质外B 与新生链结合并将其输送到膜上， 为跨膜转运做准备。 在许多方面 SecB蛋白的功能类似于信号传导所执行的功能。 靶向分泌蛋白质的新生链的识别颗粒， e 真核细胞中的内质网。 本文中描述的研究 该提案旨在分析涉及出口的分子细节， 蛋白质识别适当的细胞成分，在这种情况下，硒 B 蛋白质或包括SecB蛋白质的蛋白质复合物，以及分析 导致膜转位的后续事件。 的突变 影响SecB和输出蛋白之间或SecB和 输出装置的其它部件将被隔离和表征 此外，含有SecB的蛋白质复合物将从细胞中纯化， 提取并分析。 这些研究的第二个重点是隔离 影响其他细胞成分的突变， 与SecB类似。 蛋白质的多种事实和/或途径 已经观察到溶酶体蛋白和分泌蛋白的定位 在真核细胞中，对于原核细胞中的一些输出蛋白质， 这项工作的目标之一是阐明生物学作用， 本地化因素的复制。

Protein localization is a cellular process of fundamental importance and examples of disease syndromes in which proteins are not properly localized reveal the profound physiological consequences of failures in organelle biogenesis. In Escherichia coli, the secB gene product is involved in protein localization and promotes export of proteins out of the cytoplasm b associating with nascent chains and delivering them to the membrane, in preparation for translocation across the membrane. In many respects, the functions of the SecB protein resemble the functions performed by signal recognition particle in targeting nascent chains of secretory proteins to t e endoplasmic reticulum in eukaryotic cells. The studies described in this proposal are aimed at analysis of the molecular details involved in exporte protein recognition by the appropriate cellular components, in this case Se B protein or a protein complex including SecB protein, and the analysis of subsequent events which lead to membrane translocation. Mutations that affect interactions between SecB and exported proteins or between SecB and other components of the export apparatus will be isolated and characterized In addition, protein complexes that contain SecB will be purified from cell extracts and analyzed. A second focus of these studies is the isolation of mutations that affect other cellular components that may perform functions similar to those of SecB. Multiple facts and/or pathways for protein localization have been observed for lysosomal proteins and secreted protein in eukaryotic cells and for some of the exported proteins in prokaryotic cells and one of the goals of this work is to elucidate the biological role of the c\duplication of localization factors.