STARD3-like protein from golden noble scallop is a carotenoid transfer protein capable of binding various...

Carotenoids are hydrophobic pigments that confer coloration in marine invertebrates, but the underlying mechanisms often remain underexplored. Here, we demonstrate that the recently discovered STARD3-like protein from the selectively bred, commercially valuable golden noble scallop Mimachlamys nobilis (MnSTARD3L) contains a bona fide water-soluble carotenoid-binding domain. Using in vitro reconstitution and expression in carotenoid-synthesizing Escherichia coli, we show that the ~25-kDa START domain of MnSTARD3L binds multiple xanthophylls, including astaxanthin, zeaxanthin and canthaxanthin, inducing ~20-nm bathochromic shifts typical of functional carotenoid-protein complexes. Remarkably, MnSTARD3L preferentially accumulates the rare oxidation products, aporhodoxanthinone and trioxoeschscholtzxanthone, even in vast zeaxanthin excess. Such selectivity was rationalized by structural modeling using modern deep learning algorithms. MnSTARD3L displays no intrinsic carotenoid oxidase activity but functions as a carotenoid transfer protein, selectively donating zeaxanthin to the silkworm homolog BmCBP and aporhodoxanthinone to the unrelated cyanobacterial protein AnaCTDH. Thus, despite its acidic isoelectric point and low sequence identity with alkaline BmCBP, MnSTARD3L is also a functional carotenoid transporter, yet with distinct ligand preferences, likely dictated by peculiarities of its lipid-binding cavity and Ω1 loop. Our findings expand the repertoire of known carotenoproteins and provide mechanistic insights into how homologous protein scaffolds adapt to perform carotenoid binding and transfer functions.