真核翻译起始因子eIF-5A是普遍存在于真核细胞和古细菌中的蛋白质翻译起始因子，在细胞增殖、癌症、病毒感染及细胞凋亡等过程中发挥重要的调控功能。eIF-5A的功能发挥依赖于一种特殊的翻译后修饰- Hypusine修饰。Hypusine修饰分别由Deoxyhypusine 合酶（DSH）和Deoxyhypusine 羟化酶（DOHH）参与的两步酶促反应完成，以亚精胺为底物将eIF-5A氨基端结构域中保守的赖氨酸残基修饰为Hypusine。研究eIF-5A与DSH、DOHH的相互作用方式，将加深对Hypusine修饰的催化机制及其对eIF-5A功能调控的分子机理的理解。本项目将开展对eIF-5A与DSH、DOHH的相互作用方式的研究及复合物结构的测定，结合细胞生物学、生物化学等方法，阐明DSH、DOHH与eIF-5A相互作用并催化其Hypusine修饰的分子机理。

Eukaryotic translation initiation factor (eIF) eIF-5A is an ubiquitous protein translation initiation factor in eukaryotic cells and Archaea. It plays a critical role in regulating cell proliferation, cancer, virus infection and apoptosis. The function of eIF-5A requires an unique post-translation modification—Hypusine modification. The biosynthesis of hypusine is catalyzed from a conserved lysine in the N-terminal domain of eIF-5A and a spermidine in a two-step enzymatic reaction, which is catalyzed by Deoxyhypusine Synthase (DHS) and Deoxyhypusine hydroxylase (DOHH). Exploration of the interaction of eIF-5A with DSH and DOHH is helpful to understand the catalytic mechanism of hypusine modification and its regulation on eIF-5A function. We will study the interaction between eIF-5A, DHS and DOHH, and determine the crystal structures of the complexes, together with other biochemical and molecular biological approaches, we will illustrate the molecular mechanism of hypusine modification.