title: Calculated electrostatic gradients in recombinant human H-chain ferritin.
abstract: Calculations to determine the electrostatic potential of the iron storage protein ferritin, using the human H-chain homopolymer (HuHF), reveal novel aspects of the protein. Some of the charge density correlates well with regions previously identified as active sites in the protein. The three-fold channels, the putative ferroxidase sites, and the nucleation sites all show expectedly negative values of the electrostatic potential. However, the outer entrance to the three-fold channels are surrounded by regions of positive potential, creating an electrostatic field directed toward the interior cavity. This electrostatic gradient provides a guidance mechanism for cations entering the protein cavity, indicating the three-fold channel as the major entrance to the protein. Pathways from the three-fold channels, indicated by electrostatic gradients on the inner surface, lead to the ferroxidase center, the nucleation center and to the interior entrance to the four-fold channel. Six glutamic acid residues at the nucleation site give rise to a region of very negative potential, surrounding a small positively charged center due to the presence of two conserved arginine residues, R63, in close proximity (4.9 A), suggesting that electrostatic fields could also play a role in the nucleation process. A large gradient in the electrostatic potential at the 4-fold channel gives rise to a field directed outward from the internal cavity, indicating the possibility that this channel functions to expel cations from inside the protein. The 4-fold channel could therefore provide an exit pathway for protons during mineralization, or iron leaving the protein cavity during de-mineralization.
authors.affiliation: Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122, USA.
authors.forename: T
authors.initials: T
authors.lastname: Douglas
authors.forename: D R
authors.initials: DR
authors.lastname: Ripoll
mesh_terms: D002570:Ceruloplasmin / Q000737:chemistry; D005293:Ferritins / Q000737:chemistry*; D006801:Humans; D011994:Recombinant Proteins / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D011994:Recombinant Proteins; D005293:Ferritins; D002570:Ceruloplasmin