Zhang Chi, Zhao Shun, Li Yu-Shuai, He Chao, Wang Xiao, Liu Lin
School of Life Sciences, Anhui University, Hefei, China.
Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences, Beijing, China.
Front Plant Sci. 2022 May 23;13:899738. doi: 10.3389/fpls.2022.899738. eCollection 2022.
Plant GDP-D-mannose pyrophosphorylase (GMPase) catalyzes a committed step in ascorbic acid biosynthesis pathway. VTC1 is the first genetically characterized plant GMPase and has unique properties when compared with bacterial and animal homologs. Here we present the crystal structures of VTC1 in the unliganded and product-bound states at resolutions of 2.8 and 3.0 Å, respectively. VTC1 dimerizes in a same way like other known GMPases, but dodecamerizes in a previously unobserved arrangement. The interactions to GDP-D-mannose and inorganic pyrophosphate are revealed by the product-bound VTC1 structure. An GMPase activity assay confirms the regulatory role of the C-terminal left-handed β-helix domain, and structural analyses suggest the models of VTC1 hetero-complex with its interacting proteins. The structural information advances our insights into the different mechanisms involved in VTC1 regulation.
植物GDP-D-甘露糖焦磷酸化酶（GMPase）催化抗坏血酸生物合成途径中的一个关键步骤。VTC1是首个经遗传学鉴定的植物GMPase，与细菌和动物的同源物相比具有独特的性质。在此，我们分别展示了处于无配体状态和产物结合状态的VTC1的晶体结构，分辨率分别为2.8 Å和3.0 Å。VTC1以与其他已知GMPase相同的方式形成二聚体，但以一种先前未观察到的排列形成十二聚体。产物结合的VTC1结构揭示了其与GDP-D-甘露糖和无机焦磷酸的相互作用。一项GMPase活性测定证实了C端左手β-螺旋结构域的调节作用，结构分析提出了VTC1与其相互作用蛋白形成异源复合物的模型。这些结构信息加深了我们对VTC1调节所涉及的不同机制的理解。
