STUDIES OF LIPID-PROTEIN AND PROTEIN-PROTEIN INTERACTIONS IN HIV

我们研究了脂蛋白与蛋白质的相互作用 脂质体形成重组颗粒。多种脂蛋白 组分(极低密度脂蛋白、低密度脂蛋白、低密度脂蛋白和高密度脂蛋白)都会破坏脂质体 由一种基本不可逆的准静态计量比 进程。在高密度脂蛋白的情况下，主要的载脂蛋白A-I， 与二肉豆蔻基磷脂酰胆碱囊泡重组40：1 脂-蛋白质形成约100埃单位的圆盘 直径和厚度单位为32埃，蛋白质位于 篮筐。这些结构结果是通过组合以下各项获得的 中子散射，电子显微镜，柱层析， 以及荧光技术。 与二棕榈酰磷脂酰胆碱一起，A-I也形成我们 术语“泡状重组”颗粒 与蛋白质的生理机制有关的 组装成膜和脂蛋白。研究这一过程 我们已经开发出一种叫做“相变释放”的技术。 (PTR)也被应用于微管蛋白的掺入研究 进入细胞膜。 用荧光脂质3，3标记脂蛋白 用于研究Will细胞相互作用的双十八烷基碳菁 表面脂蛋白受体。脂蛋白也是 NBD类脂标记双色荧光鉴定 动脉粥样硬化斑块中的细胞。 统计和更通用的机械算法(HAL、HALP、 Halco)是用来评价两亲性螺旋的 结构和更一般的结构-函数关系 蛋白质和多肽。这被用来定义 关于人类白细胞抗原和人类白细胞抗原的结构和免疫原性 人类免疫缺陷病毒的包膜多聚蛋白。脂膜系统和 人类细胞分离株正被用于实验研究 特色化合成抗原性之间的相互作用 多肽和T细胞在识别过程中。结果可能是 在疫苗设计上有一定的应用。

We have investigated the interaction of lipoproteins with liposomes to form recombinant particles. A number of lipoprotein fractions (VLDL, IDL, LDL, and HDL) all disrupt liposome structure by an essentially irreversible and quasistoichiometric process. In the case of HDL, the major apoprotein, A-I, recombines with dimyristoyl phosphatidyl choline vesicles 40:1 lipid-protein to form discs approximately 100 angstrom unit in diameter and 32 angstrom unit in thickness, with protein on the rim. These structural results were obtained by a combination of neutron scattering, electron microscopy, column chromatography, and fluorescence techniques. With dipalmitoyl phosphatidylcholine, A-I also forms what we term "vesicular recombinant" particles in a process which may relate to physiological mechanisms by which proteins are assembled into membranes and lipoproteins. To study this process we have developed a technique called "phase transition release" (PTR) which is also being applied to study incorporation of tubulin into membranes. Lipoproteins were labelled with the fluorescent lipid 3,3 dioctadecylindo-carbocyanine for studies of interaction will cell surface lipoprotein receptors. The lipoproteins are also being labelled with NBD lipids for two-color fluorescence identification of cells in atheroscleroic plaques. Statistical and more general mechanical algorithms (HAL, HALP, HALCO) were devised for evaluating amphipathic helical structures and more general structure-function relationships in proteins and peptides. This is being used to define issues of structure and immunogenicity with respect to HLA antigens and to the envelope polyprotein of HIV. Lipid membrane systems and human cell isolates are being used experimentally to investigate the interaction between characterized synthetic antigenic peptides and T-cells in the recognition process. The results may have application to the design of vaccines.