Structural basis for the ligand promiscuity of the neofunctionalized, carotenoid-binding fasciclin domain protein AstaP

Fasciclins (FAS1) are ancient adhesion protein domains with no common small ligand binding reported. A unique microalgal FAS1-containing astaxanthin (AXT)-binding protein (AstaP) binds a broad repertoire of carotenoids by a largely unknown mechanism. Here, we explain the ligand promiscuity of AstaP-...

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Veröffentlicht in:Communications biology 2023-04, Vol.6 (1), p.471-471, Article 471
Hauptverfasser: Kornilov, Fedor D., Slonimskiy, Yury B., Lunegova, Daria A., Egorkin, Nikita A., Savitskaya, Anna G., Kleymenov, Sergey Yu, Maksimov, Eugene G., Goncharuk, Sergey A., Mineev, Konstantin S., Sluchanko, Nikolai N.
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Sprache:eng
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Zusammenfassung:Fasciclins (FAS1) are ancient adhesion protein domains with no common small ligand binding reported. A unique microalgal FAS1-containing astaxanthin (AXT)-binding protein (AstaP) binds a broad repertoire of carotenoids by a largely unknown mechanism. Here, we explain the ligand promiscuity of AstaP-orange1 (AstaPo1) by determining its NMR structure in complex with AXT and validating this structure by SAXS, calorimetry, optical spectroscopy and mutagenesis. α1-α2 helices of the AstaPo1 FAS1 domain embrace the carotenoid polyene like a jaw, forming a hydrophobic tunnel, too short to cap the AXT β-ionone rings and dictate specificity. AXT-contacting AstaPo1 residues exhibit different conservation in AstaPs with the tentative carotenoid-binding function and in FAS1 proteins generally, which supports the idea of AstaP neofunctionalization within green algae. Intriguingly, a cyanobacterial homolog with a similar domain structure cannot bind carotenoids under identical conditions. These structure-activity relationships provide the first step towards the sequence-based prediction of the carotenoid-binding FAS1 members. FAS1 domains, a family of cell adhesion molecules, have a carotenoid-binding function in an astaxanthin-binding protein AstaP from green algae, suggesting neofunctionalization of FAS1 in a subset of AstaP-like proteins in green algae
ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-023-04832-z