STRUCTURE AND ASSEMBLY OF COLLAGEN MOLECULES AND FIBRILS

胶原蛋白分子和原纤维的结构和组装

• 批准号: 3481402
• 负责人: ARTHUR VEIS
• 金额: $ 18.86万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-03-01 至 1994-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3481402
• 关键词: chemical aggregate; chick embryo; collagen; conformation; connective tissue disorder; connective tissue metabolism; electron microscopy; extracellular matrix; fibroblasts; fibrogenesis; immunochemistry; infrared spectrometry; interferometry; laboratory mouse; laboratory rabbit; laboratory rat; membrane proteins; messenger RNA; mucopolysaccharides; polysomes; procollagen; protein biosynthesis; protein structure; protein structure function; tissue /cell culture; translation factor

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.

I型胶原纤维构成了大多数 结缔组织，并确定其物理性质。长期的 这个项目的目标一直是了解基本事件 参与原纤维的组装和组织过程。一秒钟 目标一直是描绘前胶原蛋白组装的细节 从它们各自的PRO-α链中提取分子，并确定 管理连锁选择和注册的因素。要实现 针对这些目标，本文提出了三项具体研究。1. 前胶原分子的共翻译加工和组装。 新生的前α-链存在于复杂的多聚核糖体聚集体和 通过合成暂停来拉长。新生的链条将被分析以 确定停顿位点及其与特定序列的关系， 共翻译修饰和链关联要求。这个 多聚体聚集体在链选择和注册中的作用 被研究为与胞浆、膜蛋白和内在mRNA相关 各种因素。鸡肌腱成纤维细胞和2个仅产生 将分别对前α1链和前α2链进行研究 生物化学和电子显微镜技术。2.集结 单体胶原蛋白形成原纤维。D-周期装配由以下因素主导 端肽-螺旋受体相互作用可能涉及微妙 两个结构域的构象变化。这些文件将由 纤维形成过程中的FTIR光谱和其他物理技术 形成过程。完整和特定的阿特罗肽胶原蛋白，以及 人工合成端肽和螺旋区序列模型 将研究相互作用系统。3.原纤维的发展 组织。细胞外胶原相互作用的大分子 基质影响原纤维的结构和组织。一个理论上的 已经构建了考虑这些相互作用的框架，并 将指导EM研究检查特定基质的效果 纤维组织上的聚阴离子组分。这些研究都有 提供对连接性质的洞察的最终目标 组织功能失调。