THE MOLECULAR STRUCTURE OF COLLAGEN TYPES I AND II

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 纤维性胶原蛋白是动物细胞外基质(ECM)的基本成分，构成了所有已知哺乳动物结缔组织的结构基础：骨骼、皮肤、角膜、牙齿、肌腱、结扎、血管和淋巴管以及包括心脏和肺在内的所有器官系统。然而，尽管胶原蛋白具有重要的生物学意义，但人们对胶原蛋白的认识仅限于其三螺旋的二级结构或全纤维的重金属染色的电子显微镜图像。然而，从细胞和生物医学的角度来看，胶原蛋白结构的一个重要方面是处于中间亚纤维水平，在那里许多重要的生物过程发生在生长、发育和疾病中。这些包括但不限于：纤维形成、正常生长发育和运动后的组织重塑，以及器官系统、骨骼、软骨等建立在其上的支架，即动物身体。显然，获得(结缔组织内)胶原分子的明确和背景可视化将对科学界具有重要价值。因此，本建议的目的是：1)通过纤维结晶学对II型和I型胶原纤维的结构进行表征。2)通过纤维结晶学和生物信息学/计算方法从结构上表征通常与胶原蛋白形成络合物的细胞外基质分子的分子结构。3)发展纤维结晶学和显微X射线衍射(？XD)技术，以提高成功完成AIMS 1和AIMS 2的机会。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The fibrous collagens are the fundamental constituents of the Extracellular Matrix (ECM) of animals, forming the structural basis of all known mammalian connective tissue: bones, skin, cornea, teeth, tendons, ligature, blood and lymphatic vessels and all organ systems including the heart and lungs. Yet, despite the fundamental biological importance of collagen, the general-knowledge understanding of collagen is limited to its triple-helical 'secondary' structure or of the heavy metal stained electron microscopy images of whole fibrils A significant aspect of collagen structure from a cellular and biomedical point of view, however, is at the intermediate sub-fibrillar level, where many important biological processes occur in growth, development and disease. These include but are not limited to: fibrillogenesis, tissue remolding during normal growth and development and following exercise, and in forming the scaffolding upon which organ systems, bones, cartilage, etc., i.e. the animal body, are built upon. Clearly, obtaining an unambiguous and contextualized visualization of collagen molecules (within connective tissue) would be of significant value to the scientific community. Therefore, the aims of this proposal are to: 1) To structurally characterize the fibrillar collagens types II and I by fiber crystallography. 2) To structurally characterize the molecular organization of extracellular matrix molecules commonly found complexed with the collagens via fiber crystallography and bioinformatics / computational methods.3) To develop fiber crystallography and Micro X-ray Diffraction (¿XD) techniques that enhances the chance of successful completion of aims 1 and 2.