STRUCTURAL STUDIES OF LIPID/ PROTEIN SYSTEMS

X射线晶体学将用于研究 脂质：蛋白质复合物，其范围从细胞外蛋白质， 脂卵磷素和载脂蛋白A1到小的细胞内脂质结合蛋白。 这些研究对了解脂质的稳定性有一定的作用 沿着相关的健康问题 其涉及脂质的瞬时流动。七鳃鳗卵黄脂磷蛋白 卵母细胞是一种晶体蛋白。它含有15% w/w的 脂质目前的模型，虽然不完整，已获得的x射线 和中子衍射数据。当前的焦点是分配 氨基酸序列的电子密度图。第二项研究将 涉及载脂蛋白Al（HDL的一种成分） 和重构的载脂蛋白Al：脂质颗粒。使用现有的 重组proapo Al，新的表达系统将消除“pro” 片段并在羧基末端添加五个组氨酸残基。这将 允许简单和大规模的纯化方案。的另一方面 这些研究集中在一个细胞内脂质结合蛋白家族， 负责脂肪酸和类维生素A的转运 在细胞内。背景研究表明， 化合物包含在内部化的水填充的空腔内。研究中心- 定向诱变和晶体学将用于门控配体 结合并改变内化的结构水。 的蛋白质 以类似于脂肪酸和视黄醇的方式结合视黄酸 结合蛋白将通过X射线晶体学分析。第四 最后一项研究涉及纯化和结晶的 核受体蛋白RXR的配体结合域。的 维生素A类似物受体（RXR和RAR）在 身体计划的发展，如致畸作用所示， 胚胎这些荷尔蒙特性是对大脑的影响的结果。 特定靶基因的转录速率。虽然结构 对与DNA结合的蛋白质片段的研究已经 完成，没有维甲酸结合域的三维数据 服务器租用-美国服务租用RXR的研究与内- 细胞视黄酸结合蛋白。

X-ray crystallography will be used to study the molecular structure of lipid:protein complexes ranging from extracellular proteins such as lipovitellin and apo Al to small intracellular lipid binding proteins. All the studies play a role in understanding the stabilization of lipid in an aqueous environment along with associated health related problems which involve the transient flux of lipids. Lipovitellin from lamprey oocytes is one of the crystalline proteins. It contains 15% w/w of lipid. The present model, though incomplete, has been obtained by x-ray and neutron diffraction data. The current focus is the assignment of the amino acid sequence to the electron density map. A second study will involve crystallographic studies of both apo Al, a constituent of HDL, and reconstituted apo Al :lipid particles. Using an existing form of recombinant proapo Al, a new expression system will eliminate the "pro" piece and add five histidine residues to the carboxy-terminal. This will permit a simple and large scale purification protocol. Another aspect of the studies focusses on a family of intracellular lipid binding proteins which are responsible for the translocation of fatty acids and retinoids within the cell. The background studies have shown that the hydrophobic compound is contained within an internalized water filled cavity.. Site- directed mutagenesis and crystallography will be used to gate ligand binding and to alter the internalized structured water. A protein which binds retinoic acid in a manner analogous to the fatty acid and retinol binding proteins will be analyzed by x-ray crystallography. The fourth and last study involves the purification and crystallization of the ligand binding domain of the nuclear receptor protein, RXR. The receptors for vitamin A analogues (RXR and RAR) play a dominant role in the development of a body plan as shown by teratogenic effects in embryos. These hormonal properties are the result of effects on the transcriptional rates of special targeted genes. Although structural studies on the segment of the protein which binds to DNA have been completed, no three dimensional data on the retinoic acid-binding domain is available. Studies of RXR are closely related to those of the intra- cellular retinoic acid binding protein mentioned above.