Receptor-induced switch in site-site cooperativity during iron release by transferrin
Abstract
Iron removal by PPi from the N- and C-terminal binding sites of both free and receptor-complexed transferrin, when the partner site remains occupied with kinetically inert Co(III), has been studied at pH 7.4 and 5.6, at 25 degrees C. At extracellular pH, 7.4, the C-terminal site of free mixed-metal proteins is slightly more labile than its N-terminal counterpart in releasing iron to 0.05 M PPi. The rate and extent of iron removal are retarded from both sites when transferrins are receptor-bound. At endosomal pH, 5.6, the two sites exhibit greater kinetic heterogeneity in iron release to 0.005 M PPi. The N-terminal site is 6 times more facile in relinquishing iron than the C-terminal site when mixed-metal transferrins are free. However, the two sites are affected oppositely upon binding to the receptor. Iron release from the C-terminal site of receptor-complexed CoN-transferrin-FeC is 4 times faster than that from receptor-free protein. In contrast, iron removal from the N-terminal site of receptor-complexed FeN-transferrin-CoC is slowed by a factor of 2 compared to that from free protein. These results help explain our previous observation of a receptor-induced switch in site lability during iron removal from diferric transferrin at pH 5.6 (Bali & Aisen, 1991). Site-site cooperative interactions between the two sites of doubly-occupied transferrin during iron release are altered upon binding to receptor at pH 5.6. Iron in the otherwise weaker binding site of the N-terminal lobe is stabilized, while iron in the relatively stable binding site of the C-terminal lobe is labilized.
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Transferrin-TfR1 interaction triggers cell-mediated endocytosis of the complex and iron bound on transferrin dissociates within endosomes at a low pH (~5.5) since apotransferrin binds iron with a higher affinity at physiological pH relative to a low pH.
“Transferrin-Transferrin receptor (TfR1) interaction triggers cell-mediated endocytosis of the complex and iron bound on transferrin dissociates within endosomes at a low pH (~5.5) since apotransferrin binds iron with a higher affinity at physiological pH relative to a low pH (Bali and Aisen, 1992; Anderson and Vulpe, 2009).”
From Iron at the Centre of Candida albicans Interactions (2018) · cites this paper as Bali and Aisen, 1992
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- Authors
- Bali, P. K., & Aisen, P.
- Affiliations
- Albert Einstein College of Medicine (US)
- Venue
- Biochemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 1992-04
- Volume
- 31
- Issue
- 16
- Pages
- 3963-3967
- ISSN
- 0006-2960 (ISSN-L)
- 1520-4995
- OpenAlex
- W2062090518
- Cited by
- 53
- References
- 0
- Citations by year
- 2022: 1 · 2021: 1 · 2018: 1 · 2016: 2 · 2013: 1 · 2012: 2
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK15056, R01DK015056)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Micronutrient Interactions and Effects
- Keywords
- transferrin, iron release, receptor binding, pyrophosphate, endosomal pH, N-terminal binding site, C-terminal binding site, protein-ligand binding kinetics
- MeSH terms
- Cobalt, Humans, Hydrogen-Ion Concentration, Iron, Kinetics, Receptors, Transferrin, Transferrin
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