TARGETING AND ASSEMBLY OF E COLI OUTER MEMBRANE PROTEINS

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DESCRIPTION: The targeting and assembly of proteins are fundamental biological processes. In many instances, the targeting signal is defined by small liner stretches of sequence such as those present at the amino terminal end of secreted proteins in bacteria and eukaryotes. While these sequences in Escherichia coli assist proteins in exiting the cytoplasm, they do not determine the final location of secreted proteins within the extracytoplasmic compartments: periplasm and outer membrane. Results from this project have emphasized the view that the targeting signal for outer membrane proteins resides within the partially folded intermediates. The folding states of these intermediates are guided by the intrinsic properties of the molecule and its interactions with other cellular components including chaperone proteins and lipopolysaccharide, which is exclusively localized in the outer membrane. Novel genetic approaches outlined in this project will assist in revealing the nature of intragenic information and provide a better understanding of the dynamic interactions between various cellular components during the targeting and assembly of outer membrane proteins. Because interactions between lipidic components and proteins occur in all biological membranes, the results should have broad general interest. OmpF, OmpC and LamB will be used as model proteins. These proteins serve as the receptor for bacteriophages and form channels that allow the diffusion of water soluble solutes. Three-dimensional structures of OmpF and LamB have been resolved which, while permitting a better understanding of the structure-function relationship of these proteins, shed little light on how they reach their destination. The long term goals of this project are to understand the biogenesis of outer membrane proteins and molecular architecture of the outer membrane. These objectives will be achieved through the application of genetic approaches that are feasible and have already yielded important and new insights.