STRUCTURAL MECHANISMS OF TGF-BETA SUPERFAMILY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。骨形态发生蛋白（BMPs）是转化生长因子- β超家族的一个子集，参与多种细胞过程，包括分化、模式和细胞命运决定。当BMP配体与一种受体的细胞外结构域结合，使第二种受体结合，导致I型受体的细胞内结构域磷酸化时，信号传导被诱导。一种新发现的配体BMP-9已被证明参与胆碱能分化和葡萄糖稳态。我们最近在先进光源的光束线5.2.1处收集了中等质量的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，目的是将BMP-9与几种可用的受体胞外结构域之一结晶，以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.