The high-resolution X-ray crystallographic structure of the ferritin (EcFtnA) of Escherichia coli; Comparison with human H ferritin (HuHF) and the structures of the Fe3+ and Zn2+ derivatives

The high-resolution structure of the non-haem ferritin from Escherichia coi l (EcFtnA) is presented together with those of its Fe3+ and Zn2+ derivative s, this being the first high-resolution X-ray analysis of the iron centres in any ferritin. The binding of both metals is accompanied by small changes in the amino aci d ligand positions. Mean Fe-A(3+)-Fe-B(3+) and Zn-A(2+)-Zn-B(2+) distances are 3.24 Angstrom and 3.43 Angstrom, respectively. In both derivatives, met al ions at sites A and B are bridged by a glutamate side-chain (Glu50) in a syn-syn conformation. The Fe3+ derivative alone shows a third metal site ( Fe-C(3+)) joined to Fe-B(3+) by a long anti-anti bidentate bridge through G lu130 (mean Fe-B(3+)-Fe-C(3+) distance 5.79 Angstrom). The third metal site is unique to the non-haem bacterial ferritins. The dinuclear site lies at the inner end of a hydrophobic channel connectin g it to the outside surface of the protein shell, which may provide access for dioxygen and possibly for metal ions shielded by water. Models represen ting the possible binding mode of dioxygen to the dinuclear Fe3+ pair sugge st that a gauche mu -1,2 mode may be preferred stereochemically. Like those of other ferritins, the 24 subunits of EcFtnA are folded as four -helix bundles that assemble into hollow shells and both metals bind at din uclear centres in the middle of the bundles. The structural similarity of E cFtnA to the human H chain ferritin (HuHF) is remarkable (r.m.s. deviation of main-chain atoms 0.66 Angstrom) given the low amino acid sequence identi ty (22%). Many of the conserved residues are clustered at the dinuclear cen tre but there is very little conservation of residues making inter-subunit interactions. (C) 2001 Academic Press.