Groves M R, Hanlon N, Turowski P, Hemmings B A, Barford D
Department of Biochemistry, University of Oxford, United Kingdom.
Cell. 1999 Jan 8;96(1):99-110. doi: 10.1016/s0092-8674(00)80963-0.
The PR65/A subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit, generating functionally diverse heterotrimers. Mutations of the beta isoform of PR65 are associated with lung and colon tumors. The crystal structure of the PR65/Aalpha subunit, at 2.3 A resolution, reveals the conformation of its 15 tandemly repeated HEAT sequences, degenerate motifs of approximately 39 amino acids present in a variety of proteins, including huntingtin and importin beta. Individual motifs are composed of a pair of antiparallel alpha helices that assemble in a mainly linear, repetitive fashion to form an elongated molecule characterized by a double layer of alpha helices. Left-handed rotations at three interrepeat interfaces generate a novel left-hand superhelical conformation. The protein interaction interface is formed from the intrarepeat turns that are aligned to form a continuous ridge.
蛋白磷酸酶2A的PR65/A亚基作为一种支架分子，可协调催化亚基和可变调节性B亚基的组装，从而生成功能多样的异源三聚体。PR65的β亚型突变与肺癌和结肠癌相关。PR65/Aα亚基的晶体结构，分辨率为2.3埃，揭示了其15个串联重复的HEAT序列的构象，这些序列是存在于多种蛋白质（包括亨廷顿蛋白和输入蛋白β）中的约39个氨基酸的简并基序。单个基序由一对反平行α螺旋组成，它们以主要线性、重复的方式组装，形成一个以双层α螺旋为特征的细长分子。在三个重复序列间界面处的左旋产生了一种新型的左手超螺旋构象。蛋白质相互作用界面由重复序列内的转角形成，这些转角排列形成一条连续的脊。
