Identification of a new structural variant of human apolipoprotein E, E2(Lys146 leads to Gln), in a type III hyperlipoproteinemic subject with the E3/2 phenotype.
Identification of a new structural variant of human apolipoprotein E, E2(Lys146 leads to Gln), in a type III hyperlipoproteinemic subject with the E3/2 phenotype.
复制标题
在具有 E3/2 表型的 III 型高脂蛋白血症受试者中鉴定出人类载脂蛋白 E、E2（Lys146 导致 Gln）的新结构变体。
DOI：
10.1172/jci111085
复制
发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Blum,CB
中科院分区：
文献类型：
--
作者：
RallJr,SC;Weisgraber,KH;Innerarity,TL;Bersot,TP;Mahley,RW;Blum,CB
确定了具有载脂蛋白E（apo E）表型E3/2的III型高脂蛋白血症受试者。从等电聚焦实验结合半胱胺处理（一种测量载脂蛋白E中半胱氨酸含量的方法），该受试者的E2亚型被确定为只有一个半胱氨酸残基，与所有先前研究的E2脱辅基蛋白相反，其具有两个半胱氨酸。该单个半胱氨酸显示位于残基112处，与其在apo E3中出现的位点相同。根据氨基酸和序列分析，确定该载脂蛋白E2与载脂蛋白E3的不同之处在于残基146处存在谷氨酰胺而非赖氨酸。当测试受试者分离的E3和E2同种型的磷脂X蛋白重组体与人成纤维细胞apo-B，E受体结合的能力时，发现E3结合正常（与apo E3对照相比），但E2结合有缺陷（约为正常的40%）。虽然它们含有E3和E2，但该受试者的β-极低密度脂蛋白（β-VLDL）与E2/2 III型高脂蛋白血症受试者的β-VLDL在特征上非常相似;从每个受试者中可以获得相似的亚组分，并显示具有相似的刺激小鼠腹腔巨噬细胞中胆固醇酯蓄积的能力。在第二例III型高脂蛋白血症患者中也检测到了新的载脂蛋白E2变体。图片
A type III hyperlipoproteinemic subject having the apolipoprotein E (apo E) phenotype E3/2 was identified. From isoelectric focusing experiments in conjunction with cysteamine treatment (a method that measures cysteine content in apo E), the E2 isoform of this subject was determined to have only one cysteine residue, in contrast to all previously studied E2 apoproteins, which had two cysteines. This single cysteine was shown to be at residue 112, the same site at which it occurs in apo E3. From amino acid and sequence analyses, it was determined that this apo E2 differed from apo E3 by the occurrence of glutamine rather than lysine at residue 146. When phospholipid X protein recombinants of the subject's isolated E3 and E2 isoforms were tested for their ability to bind to the human fibroblast apo-B,E receptor, it was found that the E3 bound normally (compared with an apo E3 control) but that the E2 had defective binding (approximately 40% of normal). Although they contained E3 as well as E2, the beta-very low density lipoproteins (beta-VLDL) from this subject were very similar in character to the beta-VLDL from an E2/2 type III hyperlipoproteinemic subject; similar subfractions could be obtained from each subject and were shown to have a similar ability to stimulate cholesteryl ester accumulation in mouse peritoneal macrophages. The new apo E2 variant has also been detected in a second type III hyperlipoproteinemic subject.Images