INTERACTIONS OF FIBRONECTIN MODULES

纤维连接蛋白(FN)是一种55OkDa的糖蛋白，存在于大多数体液和 在大多数组织中形成纤维状，在那里它介导黏附，扩散和 多种细胞类型的迁移。它在胚胎发育中起着重要作用， 癌症、伤口愈合、组织重塑、造血、凝血 和纤溶作用。纤维连接蛋白还有助于去除受损的组织和凝块 吞噬细胞的循环残留物。许多细菌和寄生虫 被认为使用FN作为一种殖民组织的手段。Fn是一种“马赛克”蛋白质 由三种不同类型的同源模块(域)组成 在其他蛋白质中也有发现。这项研究的长期目标是 了解FN中每个模块的结构和功能，以了解哪些模块 一种与多种相互作用有关，哪些氨基酸 在这些部门中，这些单元直接参与了识别过程。这 将通过分离出更小的碎片来实现 重组技术，表征它们的相互作用和折叠 通过量热法和荧光法测定性能，并测定多达 关于它们的结构的可能性。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和 它转化为一种不溶于水的纤维成分 细胞外基质。此外，我们希望继续我们的角色 与选定的大分子(胶原、纤维蛋白原、 肝素、金黄色葡萄球菌多肽)，并与其他人合作，阐明 各种碎片的3D结构。所获得的知识将为 更好地理解FN的许多功能，并可能建议改进 疾病过程中的干预方法。

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.