STRUCTURAL BIOLOGY OF MACROMOLECULAR COMPLEXES

许多重要的细胞功能是由大分子执行的 复合体。这个项目的目标是阐明结构， 以及这种复合体的设计原则，重点是它们的 功能内涵。(I)噬菌体尾部纤维用于识别 易受感染的宿主细胞并引发感染。我们衍生出了一部小说 用于尾纤的三股卷绕结构 贡献多肽由短β链组成，通过以下方式连接 旋转，绕着一个共同的轴线。异常僵硬的丝状物 构象结果，其中转角提供了潜在的插入位点 用于扩展循环。(Ii)角化细胞的蛋白质组成 已发现终末分化的角质形成细胞的包膜 不同的上皮细胞之间的差异。这一变化可能提供了一种手段 调节组织细胞包膜的生物力学特性 指组织，如在复合材料中。(Iii)依赖能量的细菌 蛋白水解酶ClpAP由两个七聚体环组成的蛋白分解核心组成， 它们与ATPase的六聚体环相互作用。我们发现， 磁芯具有内腔，直径3.5 nm，容纳有源 场地，只有狭窄的通道才能进入这个会议厅，1.0- 直径1.5 nm。这些观察结果表明底物蛋白是 首先被ATPase解开，然后进入消化室。这 作用模式确保只有目标为消化的蛋白质才能 暴露在蛋白酶的活性部位。

Many important cellular functions are performed by macromolecular complexes. The goal of this project is to elucidate the structure, assembly, and design principles of such complexes with emphasis on their functional connotations. (I) Bacteriophage tail-fibers serve to recognize susceptible host cells and initiate infection. We have derived a novel three-stranded coiled-coil structure for tail-fibers in which the contributing polypeptides consist of short beta strands connected by turns, wound around a common axis. An unusually rigid filamentous conformation results, in which the turns afford potential insertion sites for extended loops. (ii) The protein composition of cornified cell envelopes of terminally differentiated keratinocytes have been found to vary between different epithelia. This variation may afford a means of modulating the biomechanical properties of the cell envelope from tissue to tissue, as in composite materials. (iii) The energy-dependent bacterial protease ClpAP consists of a proteolytic core of two heptameric rings, which interact with hexameric rings of the ATPase. We have found that the core has an internal chamber, 3.5 nm in diameter, housing the active sites, and that this chamber is accessible only by narrow channels, 1.0 - 1.5 nm in diameter. These observations imply that substrate proteins are first unfolded by the ATPase and then fed into the digestion chamber. This mode of action ensures that only proteins targeted for digestion become exposed to the active sites of the protease.