Ferritin: A biotemplate and anesthetic target

In this work we show how the ferritin family of proteins can be used as an ideal system in the fields of both nanomaterials and medicine. Ferritin assembles from 24 four-helix bundles to form a ∼500 kDa protein with an 8-nm internal cavity and an external diameter of 12 nm. First, HuHF was re-designed to facilitate noble metal ion binding, reduction, and nanoparticle formation within the cavity. A variant with 96 non-native internal cysteines promoted the formation of silver, gold, and mercury nanoparticles within the protein cavity. Second, using horse spleen apoferritin (HSAF) we also identified a fluorophore, 1-aminoanthracene (1-AMA), that is anesthetic, potentiates GABAergic transmission, and gives an appropriate dissociation constant, Kd ≈ 0.1 mM, for binding to the general anesthetic site in HSAF. Furthermore, 1-AMA reversibly immobilizes stage 45-50 Xenopus laevis tadpoles (EC50 = 16 muM) and examination by confocol microscopy indicated 1-AMA localization to brain and olfactory regions of the tadpole.