STRUCTURE DETERMINATION OF A COMPLEX OF CYTOKINE RECEPTORS AND LIGAND

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。我们对涉及GM-CSF和白细胞介素IL-3和IL-5的细胞因子受体系统信号传导的结构基础感兴趣。信号传导涉及细胞因子配体与膜结合受体的特异性结合，随后该二元复合物与另一个膜结合受体的第二次结合(b)。后一种结合事件刺激跨膜信号传导和细胞内相关的JAK/STAT激酶级联反应。这些受体是治疗过敏性疾病如哮喘的潜在药物靶点。b-common受体的x射线结构揭示了一个不寻常的联锁二聚体（Carr et al., 2001, Cell, 104, 291-300），暗示了该系统的新机制。我们已经成功地从包含所有三种信号分子（细胞因子，a受体和b受体）的细胞外成分的复合物中生产晶体。我们希望用这些晶体来测定结构。

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. We are interested in the structural basis of signalling of cytokine receptor systems involving GM-CSF and the interleukins IL-3 and IL-5. Signalling involves the specific binding of a cytokine ligand to a membrane bound a receptor, followed by a second binding of this binary complex with another membrane bound receptor (b). This latter binding event stimulates cross membrane signalling and associated JAK/STAT kinase cascades inside the cell. These receptors are potential drug targets for the treatment of allergic diseases such as asthma. The x-ray structure of the b-common receptor revealed an unusual interlocking dimer (Carr et al., 2001, Cell, 104, 291-300) suggestive of a novel mechanism in this system. We have managed to produce crystals from a complex containing the extracellular components of all three signalling molecules (cytokine, a receptor and b receptor). It is these crystals we wish to use for a structure determination.