The ability to explore, detect and modify the protein features of cell surfaces is a key in the long-term development of many diagnostic and therapeutic strategies. A major obstacle is the fact that the fundamental nature of protein-membrane interactions is largely unknown. Bacteriophage lysis genus may constitute a powerful model system for working out the physical and biochemical rules of protein-membrane interactions. Two prototype lysis genes are the S gene of lambdoid phage and the E gene of phiXl74 and related single-stranded circular DNA phage. These genes are small (typically less than or equal to 100 codons) and encode no enzymatic activity. Instead, the primary function of the products of these genes is to imbed in membranes and cause the formation of lethal membrane holes. These genes can be subjected to both positive and negative selective pressure in the laboratory and are amenable to quick sequence analysis. Mutational studies designed to determine what is important for membrane imbedding have been conducted and will be expanded. Moreover, gene fusion technology will be employed to allow purification of quantities of these proteins for direct biochemical analysis using artificial proteoliposomes. Also, the molecular basis of the """"""""clock"""""""" which schedules lysis at the end of the infective cycle will be investigated by a combination of genetic and recombinant DNA methodologies. The S gene encodes two products, one of which is an inhibitor and the other an effector of lysis, and these proteins differ only at the amino-terminus, as a result of translation initiations at two different start codons. The regulation of lysis depends at least in part on the regulation of ribosome access to these two start codons and may involve the binding of host proteins to the S mRNA. The proteins for this regulation will be identified and assigned to a bacterial gene. Also, the host gene slyD required for the formation of lysis holes by the phiX174 E protein will be characterized as to function and interaction with cell division processes.
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