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完成的