...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >Contributions of the carboxyl-terminal helical segment to the self-association and lipoprotein preferences of human apolipoprotein E3 and E4 Isoforms
【24h】

Contributions of the carboxyl-terminal helical segment to the self-association and lipoprotein preferences of human apolipoprotein E3 and E4 Isoforms

机译：羧基末端螺旋段对人载脂蛋白E3和E4同种型的自相关和脂蛋白偏好的贡献

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

To understand the molecular basis for the different self-association and lipoprotein preferences of apolipoprotein (apo) E isoforms, we compared the effects of progressive truncation of the C-terminal domain in human apoE3 and apoE4 on their lipid-free structure and lipid binding properties. A VLDL/HDL distribution assay demonstrated that apoE3 binds much better than apoE4 to HDL3, whereas both isoforms bind similarly to VLDL. Removal of the C-terminal helical regions spanning residues 273-299 weakened the ability of both isoforms to bind to lipoproteins; this led to the elimination of the isoform lipoprotein preference, indicating that the C-terminal helices mediate the lipoprotein selectivity of apoE3 and apoE4 isoforms. Gel filtration chromatography experiments demonstrated that the monomer-tetramer distribution is different for the two isoforms with apoE4 being more monomeric than apoE3 and that removal of the C-terminal helices favors the monomeric state in both isoforms. Consistent with this, fluorescence measurements of Trp-264 in single-Trp mutants revealed that the C-terminal domain in apoE4 is less organized and more exposed to the aqueous environment than in apoE3. In addition, the solubilization of dimyristoylphosphatidylcholine multilamellar vesicles is more rapid with apoE4 than with apoE3; removal of the C-terminal helices significantly affected solubilization rates with both isoforms. Taken together, these results indicate that the C-terminal domain is organized differently in apoE3 and apoE4 so that apoE4 self-associates less and binds less than apoE3 to HDL surfaces; these alterations may lead to the pathological sequelae for cardiovascular and neurodegenerative diseases.
机译：要了解载脂蛋白（APO）E同种型的不同自我关联和脂蛋白偏好的分子基础，我们比较了人ApoE3和ApoE4中的C-末端结构域的逐渐截短在无脂质结构和脂质结合特性中的影响。 VLDL / HDL分布测定结果表明，APOE3比APOE4结合到HDL3，而两种同种型类似于VLDL。去除残留物的C末端螺旋区273-299削弱了同种型与脂蛋白结合的能力;这导致消除同种型脂蛋白偏好，表明C末端螺旋介导APOE3和APOE4同种型的脂蛋白选择性。凝胶过滤色谱实验证明，单体 - 四聚体分布对于具有比ApoE3更单体的两种同种型的单体 - 四聚体分布不同，并且去除C末端螺旋在两种同种型中都有伴随着单体状态。与此一致的，单TRP突变体中TRP-264的荧光测量显示，APOE4中的C末端结构域的组织较小，更接近含水环境而不是APOE3。此外，除了与apoE3，Divyristoylphosphatidylcholine多层囊泡多层囊泡的溶解比apoe4更快;除去C末端螺旋用两种同种型显着影响溶解率。总之，这些结果表明C末端结构域在ApoE3和ApoE4中不同地组织，使得ApoE4自相互得较少并且比apoE3到HDL表面的结合。这些改变可能导致心血管和神经变性疾病的病理后遗症。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号