Acquisition of an Image Plate Area Detector for X-Ray Crystallography

申请资金用于大分子晶体结构测定的x射线数据收集系统。该仪器是R-AXIS II成像板系统，包括旋转阳极x射线发生器、聚焦镜和控制计算机。新仪器将位于加州大学伯克利分校的斯坦利大厅，并将由三个研究小组共享，这些研究小组使用x射线晶体学作为主要研究工具。目前，三个研究小组共用一个全天使用的x射线区域探测器，数据收集的积压限制了进展。这三个小组有广泛的研究兴趣。所研究的蛋白质和多肽在大小和生物学功能上存在显著差异。Alber教授提出了关于蛋白质折叠、稳定性以及分子内和分子间蛋白质相互作用的一般性问题。用于测试这些问题的模型系统包括线圈，T4溶菌酶，ATCase和转录辅助蛋白。Nelson教授研究DNA结合蛋白和蛋白质-DNA相互作用。热休克转录因子的DNA结合域晶体衍射x射线至少0.9分辨率，使其成为容易获得突变体的最高分辨率结构。史蒂文斯教授研究与神经传递有关的蛋白质。正在研究的蛋白质包括：参与儿茶酚胺生物合成的两种蛋白质，酪氨酸羟化酶和多巴胺单加氧酶；神经受体，如人类2-肾上腺素能受体、鱼类嗅觉受体、酵母因子受体；还有肉毒杆菌神经毒素。此外，除了这三个小组的个人研究兴趣外，他们还与伯克利的其他教师共同开展了晶体学合作项目。显然，一个额外的仪器将使广泛的晶体学研究取得重大进展。除了支持这三个小组的研究工作外，该仪器还将具有培训功能。其中博士后4人，研究生14人，本科生4人。联合小组的规模预计将在明年增加6名学生和研究员。

Funds are requested for an X-ray data collection system for macromolecular crystal structure determination. The instrument is the R-AXIS II imaging plate system, which includes a rotating anode X-ray generator, focusing mirrors, and a controlling computer. The new instrument will be located in Stanley Hall at the University of California, Berkeley, and will be shared by three research groups which- use X-ray crystallography as a primary research tool. Currently, the three research groups share one X-ray area detector, which is used full time, and the backlog of data collection limits progress. The three groups have a broad range of research interests. The proteins and peptides under investigation differ significantly in size and biological function. Prof. Alber asks general questions about protein folding, stability, and intra- and intermolecular protein interactions. Model systems used to test these questions include coiled-coils, T4 lysozyme, ATCase, and transcriptional accessory proteins. Prof. Nelson studies DNA binding proteins and protein-DNA interactions. Crystals of the DNA binding domain of the heat shock transcription factor diffract X-rays to at least 0.9 resolution, making this the highest resolution structure for which mutants are readily obtained. Prof. Stevens studies proteins involved in neurotransmission. Proteins under study include: two proteins involved in catecholamine biosynthesis, tyrosine hydroxylase and dopamine monoxygenase; neuroreceptors, such as human 2-adrenergic receptor, fish olfactory receptor, and yeast factor receptor; and the botulinum neurotoxin. In addition, to the individual research interests of the three groups, collaborative crystallographic projects have been initiated with other faculty at Berkeley. Clearly, an additional instrument will allow significant progress to made on a wide range of crystallographic studies. In addition to supporting the research efforts of these three groups, this instrument will have a train ing function. Between the three groups, there are 4 post-doctoral fellows, 14 graduate students, and 4 undergraduates who are pursuing crystallographic projects. The size of the joint group is expected to grow by 6 more students and fellows within the next year.