TRAF MOLECULES IN CELL SIGNALING

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。肿瘤坏死因子受体是在细胞信号转导中起重要作用的细胞因子受体。CD40是该家族中的一员，表达于B细胞上，可触发免疫反应、免疫球蛋白类别转换和激活细胞凋亡。CD40和其他TNFR，如LT？受体依赖于与TRAF蛋白的相互作用，TRAF蛋白与受体的胞内结构域结合。在以前的研究中，我们将TRAF3结合到CD40的20个残基片段中结晶。在家庭实验室中，TRAF3晶体的衍射率为3.2°。为了研究CD40和LT？R与TRAF3结合的细节，我们将受体细胞质部分的多肽浸泡到TRAF3晶体中。目前的晶体不能用标准的旋转阳极源衍射到详细结合分析所需的分辨率水平。因此，我们计划使用同步加速器x射线来收集复合体的数据。

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. CD40 and other TNFRs such as LT? receptor rely on interactions with TRAF proteins that bind to the intracellular domain of the receptor. In previous studies, we crystallized TRAF3 bound in complex to a 20-residue fragment of CD40. TRAF3 crystals diffract to 3.2 ¿¿in the home laboratory. To study the details of binding of the CD40 and Lt?R to TRAF3, we are soaking peptides from the cytoplasmic portion of the receptors into the TRAF3 crystals. The present crystals do not diffract with a standard rotating anode source to the level of resolution required for detailed binding analyses. Therefore we plan to use synchrotron x-rays to collect data for the complexes.