CONTROL OF VIRUS INDUCED LYSIS

探索、检测和修饰细胞蛋白质特征的能力 表面是许多诊断和 治疗策略 一个主要障碍是， 蛋白质-膜相互作用的基本性质在很大程度上是未知的。 噬菌体裂解属可能构成一个强大的模型系统， 研究蛋白质膜的物理和生化规律 交互. 两个原型裂解基因是类噬菌体的S基因 以及phiX 174和相关单链环状DNA噬菌体的E基因。 这些基因很小（通常小于或等于100个密码子）， 不编码酶活性。 相反， 这些基因的产物嵌入细胞膜， 致命的膜孔。 这些基因可以受到两个积极的 和负选择性压力在实验室中， 快速序列分析 突变研究旨在确定 是重要的膜嵌入已经进行，并将 扩大 此外，将采用基因融合技术， 纯化大量的这些蛋白质用于直接生物化学 使用人工脂蛋白体进行分析。 此外， 在感染周期结束时安排溶解的“时钟”将 通过基因和重组DNA的组合进行研究 方法论。 S基因编码两种产物，其中之一是 抑制剂和另一个裂解效应，这些蛋白质不同 只有在氨基末端，由于翻译起始在两个 不同的起始密码子 溶解的调节至少部分取决于 对核糖体进入这两个起始密码子的调节， 涉及宿主蛋白与S mRNA的结合。 蛋白质用于 这种调节将被鉴定并分配给细菌基因。 此外，通过对宿主基因slyD的分析，发现了该基因是形成裂解孔所必需的。 phiX 174 E蛋白将被表征为功能和相互作用 细胞分裂过程。

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.