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

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Abstract

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
JournalNature
Volume349
Issue number6309
Publication statusPublished - Feb 7 1991

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Apoferritins
Iron
X-Rays
Ceruloplasmin
Ferritins
X-Ray Diffraction
Homeostasis
Metals

ASJC Scopus subject areas

  • General

Cite this

Lawson, D. M., Artymiuk, P. J., Yewdall, S. J., Smith, J. M. A., Livingstone, J. C., Treffry, A., ... Harrison, P. M. (1991). Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts. Nature, 349(6309), 541-544.

Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts. / Lawson, David M.; Artymiuk, Peter J.; Yewdall, Stephen J.; Smith, John M A; Livingstone, J. Craig; Treffry, Amyra; Luzzago, Alessandra; Levi, Sonia; Arosio, Paolo; Cesareni, Gianni; Thomas, Christopher D.; Shaw, William V.; Harrison, Pauline M.

In: Nature, Vol. 349, No. 6309, 07.02.1991, p. 541-544.

Research output: Contribution to journalArticle

Lawson, DM, Artymiuk, PJ, Yewdall, SJ, Smith, JMA, Livingstone, JC, Treffry, A, Luzzago, A, Levi, S, Arosio, P, Cesareni, G, Thomas, CD, Shaw, WV & Harrison, PM 1991, 'Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts', Nature, vol. 349, no. 6309, pp. 541-544.
Lawson DM, Artymiuk PJ, Yewdall SJ, Smith JMA, Livingstone JC, Treffry A et al. Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts. Nature. 1991 Feb 7;349(6309):541-544.
Lawson, David M. ; Artymiuk, Peter J. ; Yewdall, Stephen J. ; Smith, John M A ; Livingstone, J. Craig ; Treffry, Amyra ; Luzzago, Alessandra ; Levi, Sonia ; Arosio, Paolo ; Cesareni, Gianni ; Thomas, Christopher D. ; Shaw, William V. ; Harrison, Pauline M. / Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts. In: Nature. 1991 ; Vol. 349, No. 6309. pp. 541-544.
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