Structural dynamics in the C terminal domain homolog of orange carotenoid Protein reveals residues critical for carotenoid uptake
Structural dynamics in the C terminal domain homolog of orange carotenoid Protein reveals residues critical for carotenoid uptake
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DOI：
10.1016/j.bbabio.2020.148214
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发表时间：
2020-08-01
影响因子：
4.3
通讯作者：
Adir, Noam
中科院分区：
文献类型：
--
作者：
Harris, Dvir;Muzzopappa, Fernando;Adir, Noam
使类胡萝卜素在自然界中的分子实体之间转运的结构特征知之甚少。在这里，我们提出了一个扩展的低聚状态的C-末端结构域同源物（CTDH）的橙子类胡萝卜素蛋白，一个关键的水溶性蛋白质在蓝藻光合光保护，在2.9埃分辨率的三维X-射线结构。这种蛋白质结合黄质类胡萝卜素配体，并在二聚体水平上进行结构重组，这有助于货物的摄取和递送。结构显示异质性，揭示了其C-末端尾部（CTT）的动态性质。基于CTDH结构的分子动力学（MD）模拟确定了控制二聚体转换机制的特定残基。基于晶体结构和这些MD模拟的诱变然后证实CTT内的这些特定残基对于类胡萝卜素摄取、封装和递送过程是关键的。我们提出了一种机制，可以应用于其他系统，需要货物摄取。
The structural features enabling carotenoid translocation between molecular entities in nature is poorly understood. Here, we present the three-dimensional X-ray structure of an expanded oligomeric state of the C-terminal domain homolog (CTDH) of the orange carotenoid protein, a key water-soluble protein in cyanobacterial photosynthetic photo-protection, at 2.9 angstrom resolution. This protein binds a canthaxanthin carotenoid ligand and undergoes structural reorganization at the dimeric level, which facilitates cargo uptake and delivery. The structure displays heterogeneity revealing the dynamic nature of its C-terminal tail (CTT). Molecular dynamics (MD) simulations based on the CTDH structures identified specific residues that govern the dimeric transition mechanism. Mutagenesis based on the crystal structure and these MD simulations then confirmed that these specific residues within the CTT are critical for carotenoid uptake, encapsulation and delivery processes. We present a mechanism that can be applied to other systems that require cargo uptake.