DELETION IN CYSTEINE-RICH REGION OF LDL RECEPTOR IMPEDES TRANSPORT TO CELL-SURFACE IN WHHL RABBIT
DELETION IN CYSTEINE-RICH REGION OF LDL RECEPTOR IMPEDES TRANSPORT TO CELL-SURFACE IN WHHL RABBIT
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DOI：
10.1126/science.3010466
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发表时间：
1986-06-06
期刊：
影响因子：
56.9
通讯作者：
RUSSELL, DW
中科院分区：
文献类型：
--
作者：
YAMAMOTO, T;BISHOP, RW;RUSSELL, DW
Watanabe遗传性高胆固醇血症（WHHL）兔是一种具有家族性高胆固醇血症的动物，其产生血浆低密度脂蛋白（LDL）的突变型受体，该受体不能以正常速率转运至细胞表面。正常和WHHL兔的互补DNA的克隆和测序表明，这种缺陷是由12个核苷酸的框内缺失引起的，该缺失从LDL受体的富含半胱氨酸的配体结合结构域中消除了4个氨基酸。通过LDL受体信使RNA的S1核酸酶图谱检测到的类似突变发生在家族性高胆固醇血症患者中，该患者的受体也未能被转运到细胞表面。这些发现表明，动物细胞可能具有故障安全机制，可以防止具有未配对或未正确键合的半胱氨酸残基的不正确折叠蛋白质的表面表达。
The Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal with familial hypercholesterolemia, produces a mutant receptor for plasma low-density lipoprotein (LDL) that is not transported to the cell surface at a normal rate. Cloning and sequencing of complementary DNA''s from normal and WHHL rabbits, shows that this defect arises from an in-frame deletion of 12 nucleotides that eliminates four amino acids from the cysteine-rich ligand binding domain of the LDL receptor. A similar mutation, detected by S1 nuclease mapping of LDL receptor messenger RNA, occurred in a patient with familial hypercholesterolemia whose receptor also fails to be transported to the cell surface. These findings suggest that animal cells may have fail-safe mechanisms that prevent the surface expression of improperly folded proteins with unpaired or improperly bonded cysteine residues.