3D structure of AstaPo1 in complex with astaxanthin carotenoid.
Newswise — AstaP – is a group of carotenoid-binding proteins, discovered recently in microalgae. The “core” of AstaP is a so-called FAS1 domain, widely spread in various species from bacteria to humans. This type of structure was previously reported only for the cell adhesion proteins, and AstaPo1 is the first protein with the novel function of FAS1 domains – carotenoid binding. Scientists from the FRC “Fundamentals of Biotechnology” and Shemyakin-Ovchinnikov Institute of bioorganic chemistry studied the 3D structure of AstaPo1 and its relationship to the protein function. The work was published in Communications Biology.
Carotenoids are powerful antioxidants that support our cells in their struggle against oxidative stress. High contents of carotenoids in diet correlates with the reduced risk of neurodegenerative, cardiovascular and ophthalmological diseases and cancers. As oxidative stress can cause or accompany the listed diseases, usage of carotenoids as antioxidants might prevent, slow down or stop the progress of the disease. However, the critically low solubility of carotenoid molecules (due to hydrophobicity) hinders their application in emerging therapies. The natural solubilizers, carotenoid-binding proteins, could solve this problem.
AstaP - is a group of carotenoid-binding proteins, discovered recently in microalgae. The “core” of AstaP is a so-called FAS1 domain, widely spread in various species from bacteria to humans. This type of structure was previously reported only for the cell adhesion proteins, and AstaPo1 is the first protein with the novel function of FAS1 domains – carotenoid binding. Besides, unlike other known carotenoid binding proteins, AstaPo1 is much more versatile: it can form complex with a variety of compounds: astaxanthin, cantaxanthin, lutein, zeaxanthin and beta-carotene.
The structure of AstaPo1 in complex with astaxanthin molecule was resolved using the NMR-spectroscopy, the approach has been never applied to the protein-carotenoid complexes.
AstaP was found to bind astaxanthin in a hydrophobic tunnel, and the tunnel length is not sufficient to accommodate the whole molecule. As a result, the terminal “rings” of carotenoid face the water, and only its fatty chain goes into the protein’s jaws. This makes the protein-ligand interaction nonspecific and explains the wide spectrum of carotenoids that can enter the protein.
The 3D structure of astaxanthin was utilized to find the features that allow FAS1 domains bind carotenoids. For this purpose, the scientists run a bioinformatics analysis, made point mutations and measured the activities of different protein variants. Mutations in the tunnel appeared to not disturb the carotenoid binding, therefore it is most likely that the secret of this function is hidden not in the tunnel properties but rather in the ligand uptake mechanism from the cell membranes. To analyze the uptake, the shortened variants of the protein were created with the deleted disordered regions, which, as was shown, do not affect the protein-carotenoid complex assembly. On the first hand, this allowed substantial reduction of the minimal size that still provides an active protein, on the other hand, the reasons why AstaPo1 is capable of carotenoid binding whereas other FAS1 proteins are not remained a mystery.
Nevertheless, the analysis of AstaPo1 structure and mobility in the absence and in the presence of astaxanthin, allowed suggesting a mechanism for the ligand uptake. Apparently the key participant of the process is a protein region, which was named a “jaw”. This “jaw”, composed of two helices, can detach from the protein molecule and apparently can sink into the membrane to bind a long chain of carotenoid.
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