INTERACTIONS OF FIBRONECTIN MODULES

纤连蛋白（Fn）是一种550 kDa的糖蛋白，存在于大多数体液中， 在大多数组织中形成纤维状，在那里它介导粘附、扩散和 多种细胞类型的迁移。它在胚胎发生中起着重要作用， 癌症，伤口愈合，组织重塑，造血，凝血 和纤维蛋白溶解。Fn还有助于清除受损组织和凝块 吞噬细胞从循环中排出的残余物。许多细菌和寄生虫 被认为是利用Fn作为组织定殖的手段。Fn是一种“镶嵌”蛋白 由三种不同类型的同源模块（结构域）组成， 也存在于其他蛋白质中。这项研究的长期目标是 了解Fn中每个模块的结构和功能，了解哪些模块是 这些氨基酸参与了多种相互作用， 在这些模块中直接参与识别过程。这 将通过分离更小的碎片来完成， 重组技术，表征它们的相互作用和折叠 性能的量热法和荧光，并确定多达 关于他们的结构可能。这个应用程序强调自我- 控制溶液中Fn超三级结构的相互作用， 其转化成不溶性纤维状组分， 细胞外基质此外，我们希望继续我们的定性 与选定的大分子（胶原，纤维蛋白原， 肝素，金黄色葡萄球菌肽），并与其他人合作阐明 各种碎片的3D结构。获得的知识将提供一个 更好地了解Fn的许多功能，并可能建议改善 干预疾病过程的方法。

Fibronectin (Fn) is a 55OkDa glycoprotein found in most body fluids and in fibrillar form in most tissues where it mediates adhesion, spreading and migration of many cell types. It plays a major role in embryogenesis, cancer, wound healing, tissue remodeling, hematopoiesis, blood coagulation and fibrinolysis. Fn also facilitates removal of damaged tissue and clot remnants from circulation by phagocytes. Many bacteria and parasites are thought to use Fn as a means of colonizing tissue. Fn is a "mosaic" protein composed of homologous modules (domains) of three different types that are also found in other proteins. The long range goal of this research is to understand the structure and function of each module in Fn, to know which ones are involved in the multiplicity of interactions and which amino acids within those modules participate directly in the recognition process. This will be accomplished by isolating ever smaller fragments by classical or recombinant techniques, characterizing their interactions and folding properties by calorimetry and fluorescence, and determining as much as possible about their structure.This application emphasizes the self- interactions that govern the supertertiary structure of Fn in solution and its transformation into an insoluble fibrillar component of the extracellular matrix. In addition we wish to continue our characterization of hetero-interactions with selected macromolecules (collagen, fibrinogen, heparin, S.aureus peptides) and to collaborate with others to elucidate the 3D structure of various fragments. The knowledge gained will provide a better understanding of the many functions of Fn and may suggest improved methods of intervention in disease processes.