Liu Ying, Zhang Yan, Wang Jia-Huai
State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing, 100871, China.
Proteins. 2014 Dec;82(12):3476-82. doi: 10.1002/prot.24702. Epub 2014 Oct 21.
Ankyrins (Ank) are a ubiquitously expressed family of multifunctional membrane adapter proteins. Ankyrin G (AnkG) is critical for assembling and maintenance of the axon initial segment. Here we present the 2.1 Å crystal structure of human AnkG death domain (hAnkG-DD). The core death domain is composed of six α-helices and three 3₁₀-helices. It forms a hydrophobic pocket on the surface of the molecule. The C-terminal tail of the hAnkG-DD curves back to have the aromatic ring of a phenylalanine residue, Phe100 insert into this pocket, which anchors the flexible tail onto the core domain. Related DDs were selected for structure comparison. The major variations are at the C-terminal region, including the α6 and the long C-terminal extension. The results of size exclusion chromatography and analytical ultracentrifugation suggest that hAnkG-DD exists as monomer in solution. Our work should help for the future investigation of the structure-function of AnkG.
锚蛋白是一类广泛表达的多功能膜适配蛋白家族。锚蛋白G（AnkG）对于轴突起始段的组装和维持至关重要。在此，我们展示了人锚蛋白G死亡结构域（hAnkG-DD）的2.1埃晶体结构。核心死亡结构域由六个α螺旋和三个3₁₀螺旋组成。它在分子表面形成一个疏水口袋。hAnkG-DD的C末端尾巴向后弯曲，使苯丙氨酸残基Phe100的芳香环插入该口袋，从而将灵活的尾巴锚定在核心结构域上。选择相关的死亡结构域进行结构比较。主要差异位于C末端区域，包括α6和长的C末端延伸部分。尺寸排阻色谱和分析超速离心结果表明，hAnkG-DD在溶液中以单体形式存在。我们的工作应有助于未来对AnkG结构功能的研究。
