TRAF MOLECULES IN CELL SIGNALING

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。肿瘤坏死因子受体是在细胞信号传导中起重要作用的细胞因子受体。CD40是该家族的一员，它在B细胞上表达并引发免疫反应、免疫球蛋白类转换和细胞凋亡的激活。像CD40一样，其他tnfr，如ltβ受体和BAFF受体，以及爱泼斯坦·巴尔病毒的癌蛋白LMP1，与TRAFs的细胞质结构域结合以刺激细胞信号。在后续的系列研究中，我们正在结晶TRAF3与这些信号伙伴的功能片段的复合物。为了研究结合的细节和定义信号传导的分子基础，将代表相互作用区域的合成肽浸泡在TRAF3晶体中。晶体通常不能与标准旋转阳极源衍射到详细结合分析所需的分辨率水平。因此，我们计划继续使用同步加速器x射线来收集复合物的数据。

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. Tumor necrosis factor receptors are cytokine receptors important in cellular signaling. CD40 is a well-characterized member of this family that is expressed on B cells and triggers immune responses, immunoglobulin class switching and activation of apoptosis. Like CD40, other TNFRs, such as LTbeta receptor and BAFF receptor, as well as the oncoprotein LMP1 from Epstein Barr Virus, associate with the cytoplasmic domain of TRAFs to stimulate cell signals. In a continuing series, we are crystallizing TRAF3 bound in complex with the functional fragments of each of these signaling partners. To study the details of binding and define the molecular basis for signaling, synthetic peptides representing the interacting regions are soaked into TRAF3 crystals. The crystals do not typically diffract with a standard rotating anode source to the level of resolution required for detailed binding analyses. Therefore we plan to continue using synchrotron x-rays to collect data for the complexes.