Biomolecular Function Research Branch, Division of Convergence Technology, Research Institute, National Cancer Center, Goyang, Gyeonggi 410-769, Korea.
J Biol Chem. 2012 Mar 30;287(14):10727-37. doi: 10.1074/jbc.M111.317594. Epub 2012 Feb 12.
Apoptosis inhibitor 5 (API5) is an anti-apoptotic protein that is up-regulated in various cancer cells. Here, we present the crystal structure of human API5. API5 exhibits an elongated all α-helical structure. The N-terminal half of API5 is similar to the HEAT repeat and the C-terminal half is similar to the ARM (Armadillo-like) repeat. HEAT and ARM repeats have been implicated in protein-protein interactions, suggesting that the cellular roles of API5 may be to mediate protein-protein interactions. Various components of multiprotein complexes have been identified as API5-interacting protein partners, suggesting that API5 may act as a scaffold for multiprotein complexes. API5 exists as a monomer, and the functionally important heptad leucine repeat does not exhibit the predicted a dimeric leucine zipper. Additionally, Lys-251, which can be acetylated in cells, plays important roles in the inhibition of apoptosis under serum deprivation conditions. The acetylation of this lysine also affects the stability of API5 in cells.
凋亡抑制因子 5（API5）是一种在各种癌细胞中上调的抗凋亡蛋白。在这里，我们呈现了人源 API5 的晶体结构。API5 呈现出细长的全α-螺旋结构。API5 的 N 端一半与 HEAT 重复序列相似，C 端一半与 ARM（角蛋白样）重复序列相似。HEAT 和 ARM 重复序列已被牵涉到蛋白-蛋白相互作用中，这表明 API5 的细胞功能可能是介导蛋白-蛋白相互作用。已经鉴定出多种多蛋白复合物的组成部分作为 API5 相互作用的蛋白伙伴，这表明 API5 可能作为多蛋白复合物的支架发挥作用。API5 以单体形式存在，而功能上重要的七肽亮氨酸重复序列不表现出预测的二聚亮氨酸拉链。此外，细胞中可以乙酰化的赖氨酸 251 在血清剥夺条件下抑制细胞凋亡中发挥重要作用。该赖氨酸的乙酰化也影响 API5 在细胞中的稳定性。
