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.
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