Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts

David M. Lawson, Peter J. Artymiuk, Stephen J. Yewdall, John M A Smith, J. Craig Livingstone, Amyra Treffry, Alessandra Luzzago, Sonia Levi, Paolo Arosio, Gianni Cesareni, Christopher D. Thomas, William V. Shaw, Pauline M. Harrison

Research output: Contribution to journalArticlepeer-review


FERRITIN is important in iron homeostasis. Its twenty-four chains of two types, H and L, assemble as a hollow shell providing an iron-storage cavity1-3. Ferritin molecules in cells containing high levels of iron tend to be rich in L chains, and may have a long-term storage function, whereas H-rich ferritins are more active in iron metabolism3-7. The molecular basis for the greater activity of H-rich ferritins has until now been obscure, largely because the structure of H-chain ferritin has remained unknown owing to the difficulties in obtaining crystals ordered enough for X-ray crystallographic analysis. Here we report the three-dimensional structure of a human ferritin H-chain homopolymer. By genetically engineering a change in the sequence of the intermolecular contact region, we obtained crystals isomorphous with the homologous rat L ferritin8,9 and of high enough quality for X-ray diffraction analysis. The X-ray structure of human H ferritin shows a novel metal site embedded within each of its four-helix bundles and we suggest that ferroxidase activity associated with this site accounts for its rapid uptake of iron10.

Original languageEnglish
Pages (from-to)541-544
Number of pages4
Issue number6309
Publication statusPublished - Feb 7 1991

ASJC Scopus subject areas

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