Johnson Hope Elizabeth, Banks Emilynn Leigh, Ozuna Ostin Samuel, Heo Jongyun
Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, Texas, USA.
Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, Texas, USA.
J Biol Chem. 2025 Jun;301(6):110269. doi: 10.1016/j.jbc.2025.110269. Epub 2025 May 21.
The small GTPases ADP-ribosylation factor (Arf), Ras, and Rho cycle between their active GTP-bound and inactive GDP-bound forms. Their regulatory proteins or inorganic redox agents regulate this cycle, which in turn regulates various important cell signals. Unlike regulatory protein-based regulation, redox-mediated regulation that occurs through the redox response of small GTPases to a redox agent is feasible only when the small GTPases are redox sensitive. The known redox-sensitive small GTPases including Ras and Rho have the reactive Cys in their unique redox motif. This study is the first to show the redox-response feature of Arf1 linked to a novel redox-sensitive Cys in the Arf-specific redox motif and its importance for cell functions. The Arf1 redox motif is currently the simplest form as it lacks the additional redox components found in Ras and Rho. The study also identifies critical radical intermediates implicated in the Arf1 redox response, along with the production of chemically modified nucleotides such as a GDP adduct. These results suggest the most elementary radical action-based mechanism for the Arf1 redox response. Although the presence of the radical intermediates was not reported, they were also suggested for the Ras and Rho redox response. Thus, the previously unknown mechanistic aspects of the Ras and Rho redox response are clarified by comparing them with those of Arf1.
小GTP酶ADP核糖基化因子（Arf）、Ras和Rho在其活性GTP结合形式与非活性GDP结合形式之间循环。它们的调节蛋白或无机氧化还原剂调节这一循环，进而调节各种重要的细胞信号。与基于调节蛋白的调节不同，通过小GTP酶对氧化还原剂的氧化还原反应而发生的氧化还原介导的调节只有在小GTP酶对氧化还原敏感时才可行。已知的对氧化还原敏感的小GTP酶，包括Ras和Rho，在其独特的氧化还原基序中有反应性半胱氨酸。本研究首次展示了Arf1与Arf特异性氧化还原基序中一个新的氧化还原敏感半胱氨酸相关的氧化还原反应特征及其对细胞功能的重要性。Arf1氧化还原基序目前是最简单的形式，因为它缺乏在Ras和Rho中发现的额外氧化还原成分。该研究还确定了与Arf1氧化还原反应有关的关键自由基中间体，以及化学修饰核苷酸如GDP加合物的产生。这些结果表明了Arf1氧化还原反应最基本的基于自由基作用的机制。虽然没有报道自由基中间体的存在，但它们也被认为与Ras和Rho的氧化还原反应有关。因此，通过将Ras和Rho的氧化还原反应与Arf1的氧化还原反应进行比较，阐明了它们以前未知的机制方面。
