The structural biology of deoxyhypusination complexes

IF 4.4 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Structure Pub Date : 2025-01-13 DOI:10.1016/j.str.2024.12.011

Elżbieta Wątor-Wilk, Piotr Wilk, Przemysław Grudnik

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Abstract

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.

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脱氧hypusination复合物的结构生物学

脱氧hypusination是独特的翻译后修饰- hypusination的第一个限速步骤，由脱氧hypusine合成酶（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。这个观点的重点是真核生物和古细菌有机体的脱氧hypusination复合物的结构生物学。基于最近发表的三种不同生物的脱氧hypusination复合物的晶体和低温电镜（cro - em）结构，我们比较了不同物种的DHS-IF5A复合物的结构特征和化学计量学。我们讨论了活性位点结构和结合界面中的保守元素，以及它们在化学计量和调节机制方面的显着差异。结构的见解提供了对脱氧假说过程的全面理解，并强调了生命领域的进化适应。未来的研究应集中在DHS活性的调控机制和不同生物中化学计量变异的功能意义上。

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来源期刊

Structure 生物-生化与分子生物学

CiteScore

8.90

自引率

1.80%

发文量

155

审稿时长

3-8 weeks

期刊介绍： Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome. In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.