STRUCTURAL MECHANISMS OF TGF-BETA SUPERFAMILY

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。骨形态发生蛋白(BMPs)是转化生长因子-β超家族的一部分，参与多种细胞过程，包括分化、构型和决定细胞命运。当BMP配体与一种受体的胞外结构域结合时，信号被诱导，使第二种类型的受体能够结合，导致I型受体的胞内结构域被磷酸化。一个新发现的配体，BMP-9，已被证明与胆碱能分化和葡萄糖稳态有关。我们最近在先进光源的5.2.1光束线上收集了中等质量的BMP-9晶体的衍射数据。我们寻求获得更高质量的数据，并扩大BMP-9结构的分辨率。我们目前正在进行结合研究，目的是使BMP-9与我们可用的几个受体胞外结构域之一结晶，以努力更好地表征这一重要蛋白质家族的结合伙伴之间的相互作用。

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. Bone Morphogenetic Proteins (BMPs), a subset of the Transforming Growth Factor-Beta superfamily, are involved in multiple cellular processes, including differentiation, patterning, and cell-fate determination. Signaling is induced when the BMP ligand binds to the extracellular domain of one type of receptor, enabling binding of a second type of receptor, resulting in the phosphorylation of the intracellular domain of the type I receptor. One newly identified ligand, BMP-9, has been shown to be involved in cholinergic differentiation and glucose homeostasis. We have recently collected diffraction data on crystals of BMP-9 of moderate quality at beam line 5.2.1 of the Advanced Light Source. We seek to obtain higher quality data and to extend the resolution for the BMP-9 structure. We are currently performing binding studies with the intent to crystallize BMP-9 with one of several receptor extracellular domains available to us in an effort to better characterize the interactions among binding partners of this important family of proteins.