MOLECULAR-MODEL OF THE A-SUBUNIT OF PROTEIN PHOSPHATASE 2A - INTERACTION WITH OTHER SUBUNITS AND TUMOR-ANTIGENS

MOLECULAR-MODEL OF THE A-SUBUNIT OF PROTEIN PHOSPHATASE 2A - INTERACTION WITH OTHER SUBUNITS AND TUMOR-ANTIGENS
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DOI:
10.1128/jvi.68.1.123-129.1994
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发表时间:
1994-01-01
影响因子:
5.4
通讯作者:
WALTER, G
WALTER, G
中科院分区:
医学2区
文献类型:
--
作者:
RUEDIGER, R;HENTZ, M;WALTER, G

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蛋白磷酸酶2A由三个亚基组成,催化亚基(C)和两个调节亚基(A和B)。A亚基具有杆状形状,由15个不相同的重复序列组成。它通过C末端的重复序列11至15结合催化亚基,并通过N末端重复序列2至8的重叠但不同的区域结合由小DNA肿瘤病毒编码的肿瘤抗原。A亚基的模型是基于不带电荷或疏水氨基酸在每个重复内的8个确定位置处保守的事实开发的。螺旋轮投影表明,每个重复序列可以排列为两个相互作用的两亲性螺旋,由一个短环连接。A亚基的突变分析显示,所提出的环对于肿瘤抗原、B亚基和C亚基的结合是重要的。体外合成的突变体A亚基的天然凝胶分析表明,以前认为包括重复2至8的B亚基的结合区域覆盖重复1至10,并且B和C亚基在与A亚基的结合中协作。
Protein phosphatase 2A consists of three subunits, the catalytic subunit (C) and two regulatory subunits (A and B). The A subunit has a rod-like shape and consists of 15 nonidentical repeats. It binds the catalytic subunit through repeats 11 to 15 at the C terminus and the tumor antigens encoded by small DNA tumor viruses through overlapping but distinct regions at N-terminal repeats 2 to 8. A model of the A subunit was developed on the basis of the fact that uncharged or hydrophobic amino acids are conserved at eight defined positions within each repeat. Helical wheel projections suggested that each repeat can be arranged as two interacting amphipathic helixes connected by a short loop. Mutational analysis of the A subunit revealed that the proposed loops are important for binding of tumor antigens, the B subunit, and the C subunit. Native gel analysis of mutant A subunits synthesized in vitro demonstrated that the binding region for the B subunit, previously thought to include repeats 2 to 8, covers repeats 1 to 10 and that the B and C subunits cooperate in binding to the A subunit.