title: Peptides selected for the protein nanocage pores change the rate of iron recovery from the ferritin mineral.
abstract: Pores regulate access between ferric-oxy biomineral inside and reductants/chelators outside the ferritin protein nanocage to control iron demineralization rates. The pore helix/loop/helix motifs that are contributed by three subunits unfold independently of the protein cage, as observed by crystallography, Fe removal rates, and CD spectroscopy. Pore unfolding is induced in wild type ferritin by increased temperature or urea (1-10 mM), a physiological urea range, 0.1 mM guanidine, or mutation of conserved pore amino acids. A peptide selected for ferritin pore binding from a combinatorial, heptapeptide library increased the rate of Fe demineralization 3-fold (p<0.001), similarly to a mutation that unfolded the pores. Conjugating the peptide to Desferal (desferrioxamine B mesylate), a chelator in therapeutic use, increased the rates to 8-fold (p<0.001). A second pore binding peptide had the opposite effect and decreased the rate of Fe demineralization 60% (p<0.001). The peptides could have pharmacological uses and may model regulators of ferritin demineralization rates in vivo or peptide regulators of gated pores in membranes. The results emphasize that small peptides can exploit the structural plasticity of protein pores to modulate function.
authors.affiliation: CHORI (Children's Hospital Oakland Research Institute) and Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Oakland, California 94609, USA.
authors.forename: Xiaofeng S
authors.initials: XS
authors.lastname: Liu
authors.forename: Leslie D
authors.initials: LD
authors.lastname: Patterson
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Miller
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Theil
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D016384:Consensus Sequence; D018360:Crystallography, X-Ray; D005293:Ferritins / Q000737:chemistry* / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000378:metabolism; D008958:Models, Molecular; D049329:Nanostructures / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary