1.A.155. The Globular Ferritin Nanopore Sensor (GFNS) Family
Traditional barrel-shaped protein channels are preferred for constructing nanopore sensors, which may miss protein candidates in non-barrel structures. Yin et al. 2025 demonstrated that globular ferritin displays excellent membrane-insertion capacity and stable transmembrane ionic current owing to its hydrophobic four-fold channels were discovered as three-fold channels. The ionic current rectification and voltage-gating characteristics are found in single-ferritin ionic current measurement. Notably, the ferritin is used as a nanopore sensor, by which high resolution discrimination of L-cysteine, L-homocysteine, and cysteine-containing dipeptides with the assistance of equivalent Cu2+. The mechanistic studies by multiple controlled experiments and quantum mechanics/all-atom/coarse-grained multiscale MD simulations revealed that analytes are synergistically captured by His114, Cys126, and Glu130 within the C3 channel, causing the current blockage signals. The promising ferritin nanopore sensor provides a guide to discovering new protein nanopores without shape restrictions (Yin et al. 2025).
Ferritin, a globular intracellular protein that acts as the main reservoir for iron, plays a role in malignancies that are associated with increased plasma ferritin concentrations. A number of studies show that tumor cells express high levels of transferrin receptors (TfR). Increased TfR expression was observed in prostate carcinoma. Apoferritin (APO) can be used as a protein nanotransporter into which a suitable medicinal substance can be encapsulated. Nanoparticles increase the permeability of tumor cells to nanotransporters and have a photothermal effect. Encapsulated doxorubicin (DOX) in APO and modification of the resulting APO/DOX with gold (AuNPs) and silver nanoparticles prepared by green synthesis increased its effectiveness (Čížek et al. 2019). Chitosan nanotransporters of anthracycline antibiotics with a zinc modified surface, for a specific interaction with metallothionein, seems to also be effective (Skaličková et al. 2017). The functionalization of gold nanoparticles on the surface of doxorubicin-encapsulated liposomes has been optimized (Choubdar et al. 2022; Torres et al. 2025).
References:
Ferritin of 173 aas and possibly 1 TMS. Globular ferritin displays excellent membrane-insertion capacity and stable transmembrane ionic current owing to its hydrophobic four-fold channels and hydrophilic three-fold channels. The ionic current rectification and voltage-gating characteristics were discovered in single-ferritin ionic current measurement (Yin et al. 2025). Notably, the ferritin was used as a nanopore sensor, by which the high resolution discrimination of L-cysteine, L-homocysteine, and cysteine-containing dipeptides with the assistance of equivalent Cu2+ was achieved. The mechanistic studies by multiple controlled experiments and quantum mechanics/all-atom/coarse-grained multiscale MD simulations reveal that analytes are synergistically captured by His114, Cys126, and Glu130 within the C3 channel, causing blockage signals. The promising ferritin nanopore sensor provides a guide to discovering new protein nanopores without shape restrictions (Yin et al. 2025).
Ferritin of Stichopus japonicus (Sea cucumber)
Ferritin, light chain of 175 aas/heavy chain of 182 aas. It stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. It also plays a role in delivery of iron to cells and mediates iron uptake in capsule cells of the developing kidney. Delivery to lysosomes by the cargo receptor NCOA4 for autophagic degradation and release or iron has been documented.
Ferritin of Equus caballus (Horse)
Ferritin, FlnA or RsgA, of 165 aas.
FlnA of E. coli