STRUCTURE AND ASSEMBLY OF COLLAGEN MOLECULES AND FIBRILS

I型胶原原纤维形成大多数胶原蛋白的主要结构元件。 结缔组织，并决定其物理特性。 长期 本项目的目标是了解基本事件 参与原纤维组装和组织过程。 第二 我们的目标是描述前胶原蛋白组装的细节， 分子从其各自的前α链，并确定 调节链选择和注册的因素。 实现 为达到这些目标，建议进行三项具体研究。 1.的 前胶原分子的共翻译加工和组装。 新生的前α链存在于复杂的多核糖体聚集体上， 延长与合成暂停。 新生链将被分析， 确定暂停位点及其与特定序列的关系， 共翻译修饰和链缔合要求。 的 多核糖体聚集体在链选择和配准中的作用将 被研究为与胞质、膜蛋白和内在mRNA相关 因素 鸡肌腱成纤维细胞和2个细胞系， 前α 1-和前α 2-链，分别将研究 生物化学和电子显微镜技术。 2.大会 将单体胶原转化为原纤维。 D-周期组装主要由 端肽-螺旋受体相互作用，这可能涉及微妙的 两个结构域的构象改变。 这些将由以下人员审查： FTIR光谱和其他物理技术在原纤维 形成过程 完整的和特异性的端肽胶原，和 合成的端肽和螺旋区序列模型 将研究互动系统。 3. 原纤维的发育 organization. 细胞外胶原相互作用大分子 基质影响原纤维结构和组织。 了理论 考虑这些相互作用的框架已经建立， 将指导EM研究检查特定基质的影响 聚阴离子组分对原纤维组织的影响。 这些研究都有 最终目的是提供对连接词性质的深入了解 组织功能障碍

Type I collagen fibrils form the principal structural elements of most connective tissues and determine their physical properties. A long term objective of this project has been to understand the basic events involved in the fibril assembly and organization processes. A second goal has been to delineate the details of the assembly of procollagen molecules from their individual pro alpha-chains and to determine the factors which regulate chain selection and registration. To achieve these objectives three specific studies are proposed. 1. The cotranslational processing and assembly of procollagen molecules. Nascent pro alpha-chains reside on complex polyribosomal aggregates and elongate with synthesis pauses. The nascent chains will be analyzed to determine pause loci and their relation to specific sequence, cotranslational modification, and chain association requirements. The role of the polysome aggregate in chain selection and registration will be studied as related to cytosolic, membrane protein, and intrinsic mRNA factors. Chick tendon fibroblasts, and 2 cell lines which produce only pro alpha 1- and pro alpha 2-chains, respectively, will be studied by biochemical an electron microscopic techniques. 2. The assembly of monomeric collagen into fibrils. D-periodic assembly is dominated by telopeptide-helix receptor interactions which may involve subtle conformational alterations in both domains. These will be examined by FTIR spectroscopy and other physical techniques during the fibril formation process. Intact and specific atelopeptide collagens, and synthetic telopeptide and helix region sequence models for the interaction systems will be studied. 3. The development of fibril organization. Collagen-interacting macromolecules of the extracellular matrix affect fibril architecture and organization. A theoretical framework for considering these interactions has been constructed and will guide EM studies examination of the effects of specific matrix polyanionic components on fibril organization. These studies all have the ultimate objective of providing insight into the nature of connective tissue dysfunctions.