The apolipoprotein B Q3405E polymorphism has no effect on its low-density-lipoprotein receptor binding affinity
Human Genetics(1996)
摘要
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.
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关键词
Arginine, Binding Affinity, Receptor Binding, Binding Assay, Population Screening
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