The apolipoprotein B Q3405E polymorphism has no effect on its low-density-lipoprotein receptor binding affinity.
The apolipoprotein B Q3405E polymorphism has no effect on its low-density-lipoprotein receptor binding affinity.
复制标题
载脂蛋白B Q3405E多态性对其低密度脂蛋白受体结合亲和力没有影响。
DOI：
10.1007/s004390050283
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发表时间：
1996
期刊：
影响因子：
5.3
通讯作者：
Kane,JP
中科院分区：
文献类型：
--
作者：
Pullinger,CR;Love,JA;Liu,W;Hennessy,LK;Ghassemzadeh,M;Newcomb,KC;Illingworth,DR;Kane,JP
通过研究载脂蛋白B100的多态性和罕见突变的影响，将更好地了解与低密度脂蛋白（LDL）受体结合的载脂蛋白B100（apoB100）序列。在重新检查apoB100 DNA测序差异后，在蛋白质的推定LDL受体结合结构域中发现了电荷变化多态性Q3405E。带正电荷的赖氨酸和精氨酸侧链的蛋白质已被证明参与配体。这使我们提出，在附近存在额外的负电荷可能会对结合亲和力产生影响。该多态性是核苷酸10422处的C到G转换的结果。人群筛选发现20个不太常见的谷氨酸等位基因，等位基因频率为0.9%。通过竞争性双标记成纤维细胞结合试验，在7个杂合子个体中研究了一个谷氨酸等位基因对LDL受体的LDL结合亲和力的影响。发现了一个谷氨酸等位基因纯合的个体，并在竞争性置换结合试验中检查了她的LDL。残基3405处的额外负电荷对结合亲和力没有可检测的影响。
A better understanding of the apolipoprotein B100 (apoB100) sequences involved in binding to the low-density lipoprotein (LDL) receptor will be achieved by studying the effects of polymorphisms and rare mutations of apoB100. Upon re-examination of apoB100 DNA sequencing discrepancies, a charge-change polymorphism, Q3405E, was found in the putative LDL receptor binding domain of the protein. Positively charged lysine and arginine side chains of the protein have been demonstrated to participate in the ligand. This led us to propose that the presence of an additional negative charge in close proximity could have an impact on the binding affinity. The polymorphism is the result of a C-to-G transition at nucleotide 10422. Population screening revealed 20 of the less common glutamate alleles at an allele frequency of 0.9%. The effect of the presence of one glutamate allele on the binding affinity of LDL for the LDL receptor was investigated in seven heterozygous individuals by a competitive dual-label fibroblast binding assay. One individual who was homozygous for the glutamate allele was discovered and her LDL examined in a competitive displacement binding assay. The additional negative charge at residue 3405 had no detectable affect on the binding affinity.