OLIGOMERIC STATE OF ERBB-FAMILY EXTRACELLULAR DOMAIN +/- ANTIBODY FRAGMENT

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。 表皮生长因子受体(EGFR，ErbB1)及其同系物被怀疑为二聚体信号状态，但单晶X射线衍射显示只有EGFR-ECD是二聚体。事实上，过度表达的erbB2(HER2)是致癌的，但即使在浓缩液中也没有发现HER2-ECD二聚体。因此，我们惊讶地在HER2-ECD/Fab37络合物的晶体中看到HER2三聚体。我们怀疑这些三聚体需要~1M磷酸盐和Fab37，但关于三聚体是存在于溶液中还是仅在晶体形成时存在的问题是一个悬而未决的问题。答案将指导我们思考我们的三聚体与膜微域中假定的高低聚状态的相关性。

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. Epidermal growth factor receptor (EGFR, erbB1) and homologues are suspected of a dimerized signaling state, but only EGFR-ecd has been seen as a dimer by single crystal x-ray diffraction. In fact, over-expressed erbB2 (HER2) is oncogenic, but no HER2-ecd dimers are seen even in concentrated solution. Thus, we are surprised to see HER2 trimers in crystals of HER2-ecd/Fab37 complex. We suspect these trimers require ~1 M phosphate and Fab37, but the question about whether trimers exist in solution or only upon crystal formation is an open one. The answer will guide thinking about the relevance of our trimers to presumed high-oligomeric states in membrane microdomains.