Wątor-Wilk Elżbieta, Wilk Piotr, Grudnik Przemysław
Małopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland; Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Kraków, Poland.
Małopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland.
Structure. 2025 Feb 6;33(2):221-227. doi: 10.1016/j.str.2024.12.011. Epub 2025 Jan 13.
Deoxyhypusination is the first rate-limiting step of the unique post-translational modification-hypusination-that is catalyzed by deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH). This modification is essential for the activation of translation factor 5A in eukaryotes (eIF5A) and Archaea (aIF5A). This perspective focuses on the structural biology of deoxyhypusination complexes in eukaryotic and archaeal organisms. Based on recently published crystal and cryogenic electron microscopy (cryo-EM) structures of deoxyhypusination complexes from three different organisms, we compare the structural features and stoichiometries of DHS-IF5A complexes across different species. We discuss conserved elements in the active site architecture and binding interfaces as well as significant differences in their stoichiometry and regulation mechanisms. The structural insights provide a comprehensive understanding of the deoxyhypusination process and highlight evolutionary adaptations across the domains of life. Future research should focus on the regulatory mechanisms governing DHS activity and the functional implications of stoichiometric variations in different organisms.
脱氧hypusination是独特的翻译后修饰——hypusination的第一步限速步骤，该修饰由脱氧hypusine合酶（DHS）和脱氧hypusine羟化酶（DOHH）催化。这种修饰对于真核生物（eIF5A）和古细菌（aIF5A）中翻译因子5A的激活至关重要。本综述聚焦于真核生物和古细菌中脱氧hypusination复合物的结构生物学。基于最近发表的来自三种不同生物体的脱氧hypusination复合物的晶体结构和低温电子显微镜（cryo-EM）结构，我们比较了不同物种中DHS-IF5A复合物的结构特征和化学计量。我们讨论了活性位点结构和结合界面中的保守元件，以及它们在化学计量和调节机制上的显著差异。这些结构见解为脱氧hypusination过程提供了全面的理解，并突出了生命各领域的进化适应性。未来的研究应聚焦于调控DHS活性的机制以及不同生物体中化学计量变化的功能影响。
