科研之友
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摘要
Eukaryotic Hferritins move iron through protein cages to form biologically required, iron mineral concentrates. The biominerals are synthesized during protein-based Fe(2+)/O(2) oxidoreduction and formation of [Fe(3+)O](n) multimers within the protein cage, en route to the cavity, at sites distributed over similar to 50 angstrom. Recent NMR and Co(2+)-protein x-ray diffraction (XRD) studies identified the entire iron path andnewmetal-protein interactions: (i) lines of metal ions in 8 Fe(2+) ion entry channels with three-way metal distribution points at channel exits and (ii) interior Fe(3+)O nucleation channels. To obtain functional information on the newly identified metal-protein interactions, weanalyzed effects of amino acid substitution on formation of the earliest catalytic intermediate (diferric peroxo-A(650 nm)) and on mineral growth (Fe(3+)O-A(350) (nm)), in A26S, V42G, D127A, E130A, and T149C. The results show that all of the residues influenced catalysis significantly (p < 0.01), with effects on four functions: (i) Fe(2+) access/selectivity to the active sites (Glu(130)), (ii) distribution of Fe(2+) to each of the three active sites near each ion channel (Asp(127)), (iii) product (diferric oxo) release into the Fe(3+)O nucleation channels (Ala(26)), and (iv) [Fe(3+)O](n) transit through subunits (Val(42), Thr(149)). Synthesis of ferritin biominerals depends on residues along the entire length of H subunits from Fe(2+) substrate entry at 3-fold cage axes at one subunit end through active sites and nucleation channels, at the other subunit end, inside the cage at 4-fold cage axes. Ferritin subunit-subunit geometry contributes to mineral order and explains the physiological impact of ferritin H and L subunits.
- 出版日期2011-7-22
