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 language | English |
|---|---|
| Pages (from-to) | 541-544 |
| Number of pages | 4 |
| Journal | Nature |
| Volume | 349 |
| Issue number | 6309 |
| Publication status | Published - Feb 7 1991 |
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Cite this
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 journal › Article
}
TY - JOUR
T1 - Solving the structure of human H ferritin by genetically engineering intermolecular crystal contacts
AU - Lawson, David M.
AU - Artymiuk, Peter J.
AU - Yewdall, Stephen J.
AU - Smith, John M A
AU - Livingstone, J. Craig
AU - Treffry, Amyra
AU - Luzzago, Alessandra
AU - Levi, Sonia
AU - Arosio, Paolo
AU - Cesareni, Gianni
AU - Thomas, Christopher D.
AU - Shaw, William V.
AU - Harrison, Pauline M.
PY - 1991/2/7
Y1 - 1991/2/7
N2 - 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.
AB - 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.
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M3 - Article
C2 - 1992356
AN - SCOPUS:0026059720
VL - 349
SP - 541
EP - 544
JO - Nature
JF - Nature
SN - 0028-0836
IS - 6309
ER -