ASSEMBLY PRINCIPLES IN GIANT RESPIRATORY PROTEINS

这项建议的总体目标是加深对 支配复杂结构最终配置的基本原则 多亚单位聚集体及其组装过程。 这种大分子组合包括核糖体、病毒、多酶 复合体、肌丝、核孔和许多其他成分 在健康问题中发挥重要作用的生物系统。许多. 这些结构是化学上对称或准对称的聚集体。 不同的亚基。无脊椎动物的巨型呼吸蛋白是 以错综复杂的对称等级构建的。这些分子 举例说明许多相当普遍的大会原则，它们将是 本次调查的主要研究对象。 拟议研究的具体目标包括理论和实践。 实验方法。(1)理论研究将涉及 自发、自限组装所需的粘合性能。 将建立适当详细的模型，以便于分析。 乙酰胆碱受体、质子ATPase和藻胆蛋白将 以及巨型血红蛋白和血蓝蛋白。(2) 实验工作将主要关注环节动物内酯的结构分析 血红蛋白。电子显微镜将用于测试在 理论研究。X射线结晶学将被用来分析 来自蚯蚓的400万道尔顿血红蛋白。(3)生化分离 以及环节动物血红蛋白独特亚结构的表征 也将进行。最后，(4)将尝试 结晶出具有良好特性的蝎子血蓝蛋白和 狼蛛。

The overall objective of this proposal is to develop an understanding of fundamental principles that govern the ultimate configuration of complex multi-subunit aggregates and the processes by which they are assembled. Such macromolecular assemblages include ribosomes, viruses, multi-enzyme complexes, muscle filaments, nuclear pores and many other components of biological systems that play important roles in health problems. Many of these structures are symmetric or quasi-symmetric aggregates of chemically distinct subunits. The giant respiratory proteins of invertebrates are constructed in an intricate hierarchy of symmetries. These molecules illustrate many rather general assembly principles and they will be principal objects of study in this investigation. The specific aims for the proposed research include both theoretical and experimental approaches. (1) The theoretical study will concern the bonding properties needed for spontaneous, self-limited assembly. Appropriately detailed models will be built to facilitate the analysis. The acetylcholine receptor, proton ATPase and phycobiliproteins will be considered as well as the giant hemoglobins and hemocyanins. (2) The experimental work will primarily concern the structure analysis of annelid hemoglobins. Electron microscopy will be used to test models developed in the theoretical study. X-ray crystallography will be used to analyze the four-million dalton hemoglobin from earthworms. (3) Biochemical isolation and characterization of distinctive substructures of annelid hemoglobins will also be carried out. Finally, (4) attempts will be made to crystallize the well characterized hemocyanins from scorpions and tarantulas.