Biophysical Properties of the Bacteriophage T4 Capsid Protein

调节亚细胞成分的大小和形状是所有细胞面临的主要问题。核糖体、肌肉粗丝和中心粒具有相对固定的尺寸，而其他成分如细胞骨架网络仅在细胞周期的特定时间具有固定的尺寸。噬菌体T4甚至头部长度的调节可以被认为是系统地探索这一问题背后的分子机制的原型，主要是因为非常明确和通用的遗传学可用。此外，对结构的生物物理学和主要衣壳蛋白的生物化学也有很多了解。头长调节有两种模型，游标模型和动力学模型。每种机制都将被测试，以确定主要头部蛋白在长度决定中的作用。为了建立一套规则来定义petite giant， ptg和petite， pt突变体中氨基酸变化的类型，研究者将在额外的ptg位点选择位点定向突变。主要衣壳蛋白gp 23的pt突变可能会增加该蛋白的“固有曲率”，从而产生比正常衣壳短的衣壳。这些实验有望产生决定性的结果。将尝试使gp 23结晶。这位研究者过去所做的工作，虽然是在不同的领域，但都很出色。Eiserling博士当然有能力开展这项工作，该计划建议给予高度优先的支持。

Regulation of the size and shape of subcellular components is a major problem faced by all cells. Ribosomes, muscle thick filaments and centrioles have relatively fixed dimensions while other components such as cytoskeletal networks have fixed dimensions only at certain times in the cell cycle. Regulation of the bacteriophage T4 even head length may be considered a prototype for systematically exploring the molecular mechanisms underlying this problem, primarily because of the extremely well defined and versatile genetics available. Furthermore, much is also known of the biophysics of the architecture, and the biochemistry of the major capsid protein. There are two models for head length regulation, the vernier and the kinetic models. Each mechanism will be tested to determine the role of the major head protein in length determination. In an attempt to establish a set of rules defining the types of amino acid changes in the petite giant, ptg and petite, pt mutants, the investigator will select site directed mutations at additional ptg site. It is possible that pt mutations in the major capsid protein gp 23 may increase the "intrinsic curvature" of this protein and hence produce shorter than normal capsids. These experiments hopefully will generate conclusive results. Attempts will be made to crystalize gp 23. The past work conducted by this investigator, although in a different area, was excellent. Dr. Eiserling is certainly capable of carrying out this work and the program recommends support with a high priority.