DIMER FORMATION BY AN N-TERMINAL COILED-COIL IN THE APC PROTEIN
DIMER FORMATION BY AN N-TERMINAL COILED-COIL IN THE APC PROTEIN
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DOI：
10.1073/pnas.90.23.11109
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发表时间：
1993-12-01
影响因子：
11.1
通讯作者：
ALBER, T
中科院分区：
文献类型：
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作者：
JOSLYN, G;RICHARDSON, DS;ALBER, T
人类APC基因的突变与结肠癌的遗传易感性有关。APC编码的多肽几乎相当于2800个氨基酸，与前900个残基的卷曲蛋白序列同源。为了确定APC蛋白的寡聚化特性，我们使用遗传和生化方法来检测APC片段的自结合能力。由APC的前55个氨基酸组成的亚结构域形成了一个稳定的、平行的、螺旋的二聚体，这与卷曲的线圈是一致的。关键二聚化元件位于蛋白质的N端，支持APC突变通过突变基因产物的二聚化发挥作用的模型。
Mutations in the human APC gene are associated with an inherited predisposition to colon cancer. APC codes for polypeptides of almost-equal-to 2800 amino acids, with sequence homologies to coiled-coil proteins in the first 900 residues. To determine the oligomerization properties of the APC protein, we used genetic and biochemical approaches to examine the ability of APC fragments to self-associate. A subdomain comprising the first 55 amino acids of APC was found to form a stable, parallel, helical dimer, as expected for a coiled coil. The location of a key dimerization element at the N terminus of the protein supports models in which mutations in APC exert effects through dimerization of the mutant gene products.