STRUCTURAL BIOLOGY OF MACROMOLECULAR COMPLEXES

大分子复合物的结构生物学

• 批准号: 2452784
• 负责人: A C STEVEN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2452784
• 关键词: active sites; adenosinetriphosphatase; bioenergetics; biomechanics; conformation; endopeptidases; enzyme substrate complex; keratinocyte; protein folding; protein structure function; structural biology; virus protein

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.

许多重要的细胞功能是由大分子 配合物这个项目的目标是阐明结构， 装配，和设计原则，这种复杂的重点， 功能内涵(I)噬菌体尾纤维用来识别 易感宿主细胞并引发感染。我们衍生出了一部小说 用于尾纤维的三股螺旋结构， 贡献多肽由短的β链组成， 绕着一个共同的轴旋转。一种异常坚硬的丝状 构象结果，其中转角提供潜在的插入位点 用于延长循环。(ii)皮质细胞的蛋白质组成 已经发现终末分化的角质形成细胞的包膜 在不同的上皮细胞中有所不同。这种变化可以提供一种方法， 调节来自组织的细胞包膜的生物力学性质 到组织中，如在复合材料中。(iii)依赖能量的细菌 蛋白酶ClpAP由两个七聚体环的蛋白水解核心组成， 其与ATP酶的六聚环相互作用。我们发现 核心具有直径为3.5 nm的内腔，容纳活性物质 现场，该会议厅只能通过狭窄的通道，1.0 - 1.5 nm的直径。这些观察结果表明，底物蛋白是 首先被ATP酶解折叠，然后送入消化室。这 作用模式确保只有针对消化的蛋白质才能 暴露于蛋白酶的活性位点。