Gram-negative bacterial cells are surrounded by a double layer of membranes, i.e., the outer membrane and the inner, cytoplasmic membrane. The outer membrane is in many ways an ideal biological membrane for study, because its composition as well as functions are quite simple. The major advances in this field has been the discovery of porins, membrane proteins forming nonspecific channels for the diffusion of any small, hydrophilic solutes, as well as at least one membrane protein shown to form a configurationally specific channel. The major objectives of this project is to understand the structure-function relationship in this simple membrane, as well as mechanisms of its assembly. Special emphasis will be placed on the following areas. (1) Structure of porin and the properties of the channel. These are important because practically all antibiotics and chemotherapeutic agents must diffuse through these channels before they reach their targets, and the properties of the channel are major factors that affect the barrier properties of the outer membrane. (2) Structure-function relationship in specific channels, as a model for the central unit in any specific membrane transport systems. (3) Permeability of the non-protein regions of the outer membrane. This is again an important factor in determining the barrier properties of the membrane. (4) Selected aspects of the membrane biogenesis, including the cell cycle dependence of the synthesis or insertion of certain proteins.
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