A Photoactive Carbon-Monoxide-Releasing Protein Cage for Dose-Regulated Delivery in Living Cells.
Protein cages can serve as bioinorganic molecular templates for functionalizing metal compounds to regulate cellular signaling. We succeeded in developing a photoactive CO-releasing system by constructing a composite of ferritin (Fr) containing manganese-carbonyl complexes. When Arg52 adjacent to Cys48 of Fr is replaced with Cys, the Fr mutant stabilizes the retention of 48 Mn-carbonyl moieties, which can release the CO ligands under light irradiation, although wild-type Fr retains very few Mn moieties. The amount of released CO is regulated by the extent of irradiation. This could reveal an optimized dose for cooperatively activating the nuclear factor κB (NF-κB) in mammalian cells and the tumor necrosis factor α (TNF-α). These results suggest that construction of a CO-releasing protein cage will advance of research in CO biology.
Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B-55, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan.
Kenta
K
Fujita
Chemical Resources Laboratory, Tokyo Institute of Technology, R1-27, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8503, Japan.
Yuya
Y
Tanaka
Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B-55, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan.
Satoshi
S
Abe
Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B-55, 4259 Nagatsuta-cho, Midori-ku, Yokohama, 226-8501, Japan. tueno@bio.titech.ac.jp.
Takafumi
T
Ueno
D002248:Carbon Monoxide / Q000737:chemistry*; D004337:Drug Carriers; D011506:Proteins / Q000737:chemistry*
D004337:Drug Carriers; D011506:Proteins; D002248:Carbon Monoxide
bioinorganic chemistry; carbon monoxide; metalloproteins; photoactivation; protein engineering