STRUCTURAL STUDIES OF LIPID:PROTEIN SYSTEMS

脂质：蛋白质系统的结构研究

• 批准号: 3268570
• 负责人: LEONARD J. BANASZAK
• 金额: $ 29.05万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-05-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3268570
• 关键词: X ray crystallography; adipose tissue; blood lipoprotein metabolism; chemical structure function; conformation; cytoplasm; enzyme biosynthesis; enzyme structure; fatty acid binding protein; lipids; malate dehydrogenase; membrane proteins; membrane reconstitution /synthesis; mitochondria; nonblood lipoprotein; oxidoreductase; protein structure; protein transport; site directed mutagenesis; vitellin

Macromolecular structures will be obtained by x-ray crystallography and this data will be used to study structure/function relationships for biological systems containing both proteins and lipids. Several different proteins have already been crystallized and partially analyzed. The first, lipovitellin, is a lipoprotein containing -15% w/w of bound phospholipid. this ongoing project has taken on added interest with the discovery that the amino acid sequence of lipovitellin is in part related to that of apob100, a protein associated with human serum LDL. Levels of LDL correlate with a variety of cardiovascular diseases, particularly atherosclerosis. The second project involves structural studies of fatty acid binding proteins (FABPs). These small proteins are members of a larger family of structurally similar molecules responsible for either intracellular shuttling or extracellular transport of fatty acids or other water insoluble ligands. In some cells such as adipocytes, regulation of fat mobilization occurs through several different mechanisms. One appears to be under the influence of insulin and its receptor, and involves phosphorylation of adipocyte FABP. This may be the reaction which regulates lipid mobilization in fat tissue. Using x-ray analysis, the structure of recombinant liver and adipocyte FABP will be determined. In a related focussing of changing the protein conformation to a form which has some catalytic esterase activity. The third project involves single crystal x-ray studies of another recombinant protein, the precursor form of mitochondrial malate dehydrogenase, premMDH. PremMDH is the form of malate dehydrogenase which is biosynthesized in cytosol. By some unknown mechanism it is recognized by and translocated to the inner membrane matrix of mitochondria. At that point, a proteolytic reaction occurs and the mature form of malate dehydrogenase (-22 amino acids from the NH2-terminal) is formed. The important biological questions center on the structural basis for the recognition and translocation process. The latter involves passage through bilayer lipid.

大分子结构将通过X射线晶体学获得， 这些数据将用于研究结构/功能关系， 含有蛋白质和脂质的生物系统。 几种不同 蛋白质已经被结晶并被部分分析。 第一， 卵黄脂磷蛋白是含有~ 15%w/w结合磷脂的脂蛋白。 这个正在进行的项目增加了人们的兴趣， 卵黄脂磷蛋白的氨基酸序列部分地与 apob 100是一种与人血清LDL相关的蛋白质。 水平ldl 与多种心血管疾病相关， 动脉粥样硬化 第二个项目涉及脂肪酸的结构研究 酸结合蛋白（FABP）。 这些小蛋白质是一个 一个结构相似的分子大家族， 细胞内穿梭或细胞外转运脂肪酸或其他 水不溶性配体。 在一些细胞如脂肪细胞中， 脂肪动员通过几种不同的机制发生。 一个似乎 受胰岛素及其受体的影响， 脂肪细胞FABP的磷酸化。 这可能是反应， 调节脂肪组织中的脂质动员。 使用X射线分析， 将测定重组肝和脂肪细胞FABP的结构。 中 将蛋白质构象改变为具有以下特征的形式的相关焦点： 一些催化酯酶活性。 第三个项目涉及单一 另一种重组蛋白的晶体X射线研究， 线粒体苹果酸脱氢酶。 PremMDH是苹果酸的形式 脱氢酶，其在胞质溶胶中生物合成。 被不知名的 它被识别并转移到内膜基质的机制 of mitochondria线粒体. 此时，发生蛋白水解反应， 成熟形式的苹果酸脱氢酶（从NH 2末端起约22个氨基酸） 形成有 重要的生物学问题集中在 识别和易位过程的基础。 后者涉及 通过双层脂质。