Metal-induced Conformational Changes in Transferrins
Abstract
Recent studies on iron-loaded transferrins have revealed a conformational change upon binding iron due to a domain closure. It has been suggested that the domain closure may be the key for the receptor recognition of the metal loaded transferrin (Grossmann et al., 1992). Small angle X-ray scattering has been used to provide direct structural information on the conformational changes that may take place upon the binding and release of different metals to the transferrins in solution. The data show that In3+ and Cu2+ induce the same domain closure as Fe3+; Al3+ causes a conformational change of somewhat smaller magnitude while Hf4+ does not induce any conformational change. The results are discussed in terms of the molecular recognition of metal loaded transferrin by the receptor.
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DMT1 expression was increased by an iron-deficient diet, and it was highly expressed in the rat duodenum.
“Its expression was increased by an iron-deficient diet, and it was highly expressed in the rat duodenum.”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [117]
DMT1 is critical to the export of iron released from Tf in the acidic endosome into the cytosol.
“DMT1 is critical to the export of iron released from Tf in the acidic endosome into the cytosol (see Fig. 1) (117).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [117]
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Yajima, H., Yamamoto, H., Nagaoka, M., et al. (1998) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(98)00014-2 · Cited by 9 · see citing works
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Profitt, L. A., Baxter, R. H. G., & Valentine, A. M. (2022) · Biochemistry · doi:10.1021/acs.biochem.1c00813 · Cited by 6 · see citing works
Hayashi, K., Longenecker, K. L., Liu, Y.-L., Faust, B., Prashar, A., Hampl, J., Stoll, V. S., & Vivona, S. (2021) · Scientific Reports · doi:10.1038/s41598-020-79090-8 · Cited by 8 · see citing works
Saponja, J. A., & Vogel, H. J. (2011) · Canadian Journal of Chemistry · doi:10.1139/v11-019 · Cited by 5 · see citing works
Nisar, S., & Kazmi, S. A. (2010) · Spectrochimica Acta Part A Molecular and Biomolecular Spectroscopy · doi:10.1016/j.saa.2010.08.020 · Cited by 4 · see citing works
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Smith, C. A. (2004) · Handbook of Metalloproteins · doi:10.1002/0470028637.met159 · Cited by 1 · see citing works
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Starreveld, J. S. (1994) · RePub (Erasmus University Rotterdam)
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Testa, U. (2001) · CRC Press eBooks · doi:10.1201/b14262-5
Smith, C. A. (2004) · Encyclopedia of Inorganic and Bioinorganic Chemistry · doi:10.1002/9781119951438.eibc0586 · Cited by 1 · see citing works
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Bardou‐Jacquet, E. (2013) · theses.fr (ABES) · doi:10.70675/99eb557fz5edcz4fdezbd26z84ca08eab5aa
- Authors
- Grossmann, J. G., Neu, M., Evans, R. W., Lindley, P. F., Appel, H., & Hasnain, S. S.
- Affiliations
- Karlsruhe Institute of Technology (DE)
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 1993-02
- Volume
- 229
- Issue
- 3
- Pages
- 585-590
- ISSN
- 0022-2836 (ISSN-L)
- OpenAlex
- W1985317971
- Cited by
- 67
- References
- 0
- Citations by year
- 2025: 1 · 2022: 2 · 2021: 3 · 2019: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 1
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
- Keywords
- transferrin, domain closure, metal ion binding, indium, copper, aluminum, hafnium, protein solution structure
- MeSH terms
- Metals, Protein Conformation, Scattering, Radiation, Solutions, Transferrin
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