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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 富含亮氨酸的小重复序列蛋白（SLRP）是一大类糖蛋白，在伤口愈合、退行性疾病和癌症领域具有相当大的医学应用。蛋白聚糖通常通过与细胞外基质中的其他蛋白质结合来发挥其功能。SLRP的蛋白质核心的独特结构显示由亮氨酸重复形成的β链的超螺旋。独特的区域在两端覆盖伸长的分子。SLRP是高度糖基化的分子，在生物化学和结晶方面都很难处理。这些分子很少容易或容易从细菌表达系统中获得。为了理解这些分子的结构和生物学功能之间的关系，我们正在研究这个蛋白聚糖家族的所有代表性成员的晶体结构。我们已经确定了核心蛋白聚糖和双糖蛋白聚糖的蛋白质核心的晶体结构，最近还获得了光蛋白聚糖的衍射质量晶体。从小角X射线散射的核心蛋白聚糖的溶液结构也得到了验证的核心蛋白聚糖晶体结构的一些结论。

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.