STRUCTURE AND FUNCTION OF SMALL LEUCINE-RICH REPEAT PROTEOGLYCANS (SLRPS)

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。 富含亮氨酸的小重复蛋白(SLRPs)是一大类糖蛋白，在伤口愈合、退行性疾病和癌症等领域具有重要的医疗应用价值。蛋白多糖通常通过与细胞外基质中的其他蛋白质结合来发挥作用。SLRPs蛋白质核心的独特结构显示了由亮氨酸重复形成的β链的超级螺旋。独特的区域覆盖着两端细长的分子。SLRP是高度糖基化的分子，很难处理，无论是出于生化目的还是出于结晶目的。这些分子中很少有容易或容易从细菌表达系统获得的。为了了解这些分子的结构和生物功能之间的关系，我们正在研究这个蛋白多糖家族中所有有代表性的成员的晶体结构。我们已经测定了核心蛋白聚糖和二聚糖的晶体结构，最近还获得了具有衍射性的鲁米肯晶体。通过小角X射线散射得到了核心蛋白聚糖的溶液结构，验证了核心蛋白聚糖晶体结构的部分结论。

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. Small Leucine-Rich Repeat proteins (SLRPs) are a large group of glycoproteins with considerable medical applications in areas of wound healing, degenerative diseases and cancer. The proteoglycans usually exert their function through the binding of other proteins within the extra-cellular matrix. The unique structures of the protein cores of the SLRPs show a super helix of beta strands formed by the leucine repeats. Unique regions are capping the elongated molecules at both ends. The SLRPs are heavily glycosylated and difficult molecules to work with, both biochemically and for crystallization purposes. Few of these molecules are easily or readily available from bacterial expression systems. In an effort to understand the relationship between the structure and the biological function of these molecules we are pursuing crystal structures of all representative members of this family of proteoglycans. We have determined crystal structures of the protein cores of decorin and biglycan and also recently obtained diffraction quality crystals of lumican. A solution structure of decorin from small angle x-ray scattering was also obtained to verify some of the conclusions from the decorin crystal structure.