Photoswitchable Isoprenoid Lipids Enable Optical Control of Peptide Lipidation.
Photoswitchable Isoprenoid Lipids Enable Optical Control of Peptide Lipidation.
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DOI：
10.1021/acschembio.2c00645
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发表时间：
2022-10-21
影响因子：
4
通讯作者：
Distefano, Mark D.
中科院分区：
文献类型：
--
作者：
Morstein, Johannes;Bader, Taysir;Cardillo, Ariana L.;Schackmann, Julian;Ashok, Sudhat;Hougland, James L.;Hrycyna, Christine A.;Trauner, Dirk H.;Distefano, Mark D.
可拍摄的脂质已成为脂质生物活性，代谢和生物物理特性的光学控制的吸引人工具。它们的设计通常基于将偶氮苯照片开关掺入疏水性脂质尾巴中，可以使用两种不同的波长光线在其反式和顺式形式之间切换。尽管已成功设计甘油和鞘脂，但尚未研究异磷酸脂质。在本文中，我们描述了类异胞素脂质的可拍打类似物的发展，并系统地评估了它们在酿酒酵母中CAAX蛋白质中各种步骤的光学控制的潜力。 Farnesyl二磷酸（AZOFPP-1）的一个可拍打的类似物可以有效地通过Farnesyltransferase对底物原始化的光学控制。异丙肾上腺素加工的随后步骤（Ste24或RCE1的蛋白水解和Ste14的羧基甲基化的蛋白水解）受到引入底物A因子脂质部分的光异构化的影响，这是一种来自酵母的底物A因子的脂质部分。我们在体外评估了A因子类似物的蛋白水解和甲基化，并评估了包含Photoswitch的全面处理的A因子类似物的生物活性，外源添加到同源酵母菌细胞中。这些数据结合在一起，描述了类异on-脂质的第一个成功转化为光脂，并提出了这种方法来对蛋白质前化的光学控制方法。
Photoswitchable lipids have emerged as attractive tools for the optical control of lipid bioactivity, metabolism, and biophysical properties. Their design is typically based on the incorporation of an azobenzene photoswitch into the hydrophobic lipid tail, which can be switched between its trans- and cis-form using two different wavelengths of light. While glycero- and sphingolipids have been successfully designed to be photoswitchable, isoprenoid lipids have not yet been investigated. Herein, we describe the development of photoswitchable analogs of an isoprenoid lipid and systematically assess their potential for the optical control of various steps in the isoprenylation processing pathway of CaaX proteins in Saccharomyces cerevisiae. One photoswitchable analog of farnesyl diphosphate (AzoFPP-1) allowed effective optical control of substrate prenylation by farnesyltransferase. The subsequent steps of isoprenylation processing (proteolysis by either Ste24 or Rce1 and carboxyl methylation by Ste14) were less affected by photoisomerization of the group introduced into the lipid moiety of the substrate a-factor, a mating pheromone from yeast. We assessed both proteolysis and methylation of the a-factor analogs in vitro and the bioactivity of a fully processed a-factor analog containing the photoswitch, exogenously added to cognate yeast cells. Combined, these data describe the first successful conversion of an isoprenoid lipid into a photolipid and suggest the utility this approach for the optical control of protein prenylation.
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DOI：
10.1073/pnas.0704212104
发表时间：
2007-08-14
影响因子：
11.1
作者：
Coffinier, Catherine;Hudon, Sarah E.;Fong, Loren G.
通讯作者：
Fong, Loren G.
影响因子：
3.6
作者：
Gaon, I;Turek, TC;Distefano, MD
通讯作者：
Distefano, MD
影响因子：
2.9
作者：
Dolence, JM;Cassidy, PB;Poulter, CD
通讯作者：
Poulter, CD
影响因子：
15
作者：
Doroudgar, Mahmoudreza;Morstein, Johannes;Glaubitz, Clemens
通讯作者：
Glaubitz, Clemens
影响因子：
2.9
作者：
Gangopadhyay, Soumyashree A.;Losito, Erica L.;Hougland, James L.
通讯作者：
Hougland, James L.