title: Calculation of iron transport through human H-chain ferritin.
abstract: Influx of ferrous ions from the cytoplasm through 3-fold pores in the shell of ferritin protein is computed using a 3-dimensional Poisson-Nernst-Planck electrodiffusion model, with inputs such as the pore structure and the diffusivity profile of permeant Fe(2+) ions extracted from all-atom molecular dynamics (MD) simulations. These calculations successfully reproduce experimental estimates of the transit time of Fe(2+) through the ferritin coat, which is on the millisecond time scale and hence much too long to be directly simulated via all-atom MD. This is also much longer than the typical time scale for ion transit in standard membrane spanning ion channels whose pores bear structural similarity to that of the 3-fold ferritin pore. The slow time scale for Fe(2+) transport through ferritin pores is traced to two features that distinguish the ferritin pore system from standard ion channels, namely, (i) very low concentration of cytoplasmic Fe(2+) under physiological conditions and (ii) very small internal diffusion coefficients for ions inside the ferritin pore resulting from factors that include the divalent nature of Fe(2+) and two rings of negatively charged amino acids surrounding a narrow geometric obstruction within the ferritin pore interior.
authors: Department of Chemistry, University of Pittsburgh , Pittsburgh, Pennsylvania 15260, United States.
authors: Rozita
authors: R
authors: Laghaei
authors: William
authors: W
authors: Kowallis
authors: Deborah G
authors: DG
authors: Evans
authors: Rob D
authors: RD
authors: Coalson
mesh_terms: D001052:Apoferritins / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004058:Diffusion; D006801:Humans; D017136:Ion Transport; D007477:Ions / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D055672:Static Electricity; D014867:Water / Q000737:chemistry
chemical_list: D007477:Ions; D014867:Water; D001052:Apoferritins; D007501:Iron