Fundamental mechanisms and application aspects of protein-mediated carotenoid transport
蛋白质介导的类胡萝卜素转运的基本机制和应用方面
基本信息
- 批准号:429542475
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:2020
- 资助国家:德国
- 起止时间:2019-12-31 至 2022-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Carotenoids abound in photosynthetic organisms and are essential nutrients for animals. The more than 700 species perform multifaceted functions ranging from coloration, energy harvesting and excitation energy dissipation in photosynthesis, light protection and antioxidant activity, and they are precursors for vitamins, visual pigments and hormones. Though carotenoids are hydrophobic and partition into lipid compartments or membranes, only very few specific carotenoid-binding proteins are known, which keep carotenoids in water-soluble form to shuttle them between membranes, between carotenoproteins or between cells in the organism. One of these examples is the 35-kDa Orange Carotenoid Protein (OCP), which plays a central role in cyanobacterial photoprotection. Upon illumination with blue light, OCP is photoconverted from the basic, orange form OCPo into the red signaling form OCPr, the latter quenching the fluorescence of phycobilisome (PBs) antennae, thus preventing excessive energy flow to the photosystems to enact non-photochemical quenching (NPQ).During our studies on a series of OCP variants, we discovered that carotenoids can be transferred between the isolated domains of OCP. Biochemical and spectroscopic data hinted at several intermediates of this process suggesting a multi-step nature of this unique carotenoid transfer mechanism. It was later shown that naturally occurring homologs of the OCP C-terminal domain (CTDH proteins) are able to regulate photoprotection in several cyanobacteria lacking full-length OCP by transferring the carotenoid from membranes to homologs of the OCP N-terminal domain (HCP proteins), which are constantly able to quench PBs fluorescence. This novel type of regulation of photosynthetic activity is only superficially studied yet. Given the huge number of CTDHs with vastly different sequences, as well as the existence of eukaryotic proteins, which are similar to CTDHs in spatial structure (nuclear transport factor 2 [NTF-2] family), the principles of protein-mediated carotenoid transport can be explored in detail. We have shown that various CTDH proteins specifically bind certain types of carotenoids, which strongly influences the spectral and structural properties, and the interaction of CTDH proteins with membranes. Since other NTF-2-like proteins specifically bind carotenoids as well (e.g. the lutein-binding StARD3 protein in primate retinae), the identification of common mechanisms of carotenoid transport systems is within reach. This project aims to explore these fundamental features of protein-mediated carotenoid transport and establish the overarching functional principles in molecular detail, taking benefit from a multidisciplinary, systemic approach (biochemistry, biophysics, structural and molecular biology, steady-state and time-resolved spectroscopy). As a project result, the potentials for using CTDH and HCP protein variants as modules for the targeted delivery of antioxidants will be explored.
类胡萝卜素在光合生物中含量丰富,是动物必需的营养素。700多个物种执行多方面的功能,从着色,能量收集和光合作用中的激发能量耗散,光保护和抗氧化活性,它们是维生素,视色素和激素的前体。虽然类胡萝卜素是疏水性的,并分配到脂质区室或膜,只有很少的特定的类胡萝卜素结合蛋白是已知的,它保持类胡萝卜素在水溶性形式,以穿梭它们之间的膜,胡萝卜素蛋白或细胞之间的生物体。这些例子之一是35-kDa的橙子类胡萝卜素蛋白(OCP),它在蓝藻光保护中起着核心作用。在蓝光照射下,OCP从基本的橙子形式OCPo光转化为红色信号形式OCPr,后者猝灭藻胆体(phycobilisome,PBs)触角的荧光,从而阻止过多的能量流到光系统中产生非光化学猝灭(non-photochemical quenching,NPQ)。生化和光谱数据暗示了这个过程中的几个中间体,表明这种独特的类胡萝卜素转移机制的多步骤性质。后来表明,天然存在的同源物的OCP C-末端结构域(CTDH蛋白)能够调节光保护在几个蓝藻缺乏全长OCP通过转移类胡萝卜素从膜的同源物的OCP N-末端结构域(HCP蛋白),这是不断能够淬灭PB荧光。这种新型的光合作用活性调节只是表面上的研究。由于CTDH的数量巨大,序列差异很大,以及真核蛋白的存在,这是类似于CTDH的空间结构(核转运因子2 [NTF-2]家族),蛋白质介导的类胡萝卜素运输的原则可以详细探讨。我们已经表明,各种CTDH蛋白特异性结合某些类型的类胡萝卜素,这强烈影响光谱和结构特性,以及CTDH蛋白与膜的相互作用。由于其他NTF-2样蛋白也特异性结合类胡萝卜素(例如灵长类动物视网膜中的叶黄素结合StARD3蛋白),因此类胡萝卜素转运系统的常见机制的鉴定是可以实现的。该项目旨在探索蛋白质介导的类胡萝卜素运输的这些基本特征,并建立分子细节的总体功能原则,从多学科,系统的方法(生物化学,生物物理学,结构和分子生物学,稳态和时间分辨光谱学)中获益。作为一个项目的结果,将探讨使用CTDH和HCP蛋白变体作为抗氧化剂靶向递送模块的潜力。
项目成果
期刊论文数量(0)
专著数量(0)
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Professor Dr. Thomas Friedrich其他文献
Professor Dr. Thomas Friedrich的其他文献
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{{ truncateString('Professor Dr. Thomas Friedrich', 18)}}的其他基金
Dynamic structural changes of the photoactive orange carotenoid protein
光活性橙色类胡萝卜素蛋白的动态结构变化
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379950877 - 财政年份:2018
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