The unique kinetics of iron release from transferrin: the role of receptor, lobe-lobe interactions, and salt at endosomal pH.

Journal of Molecular Biology
Shaina L ByrneAnne B Mason

Abstract

Transferrins are a family of bilobal iron-binding proteins that play the crucial role of binding ferric iron and keeping it in solution, thereby controlling the levels of this important metal. Human serum transferrin (hTF) carries one iron in each of two similar lobes. Understanding the detailed mechanism of iron release from each lobe of hTF during receptor-mediated endocytosis has been extremely challenging because of the active participation of the transferrin receptor (TFR), salt, a chelator, lobe-lobe interactions, and the low pH within the endosome. Our use of authentic monoferric hTF (unable to bind iron in one lobe) or diferric hTF (with iron locked in one lobe) provided distinct kinetic end points, allowing us to bypass many of the previous difficulties. The capture and unambiguous assignment of all kinetic events associated with iron release by stopped-flow spectrofluorimetry, in the presence and in the absence of the TFR, unequivocally establish the decisive role of the TFR in promoting efficient and balanced iron release from both lobes of hTF during one endocytic cycle. For the first time, the four microscopic rate constants required to accurately describe the kinetics of iron removal are reported for hTF with and ...Continue Reading

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Citations

Jul 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Brian E EckenrothAnne B Mason
Nov 19, 2013·PLoS Computational Biology·Simon Mitchell, Pedro Mendes
Oct 25, 2012·Annual Review of Physiology·Tobias Stauber, Thomas J Jentsch
May 23, 2014·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Sandeep KumarRajesh Kumar
Mar 22, 2012·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Ryan C McCarthy, Daniel J Kosman
Aug 17, 2010·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Ashley N SteereAnne B Mason
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Aug 23, 2011·Biochimica Et Biophysica Acta·Alex D SheftelPrem Ponka
Jun 28, 2011·Biochimica Et Biophysica Acta·Ashley N SteereAnne B Mason
Mar 21, 2015·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Haleh AbdizadehCanan Atilgan
Aug 19, 2011·Biochimica Et Biophysica Acta·Wesley R Harris
Aug 30, 2011·Biochimica Et Biophysica Acta·Jean-Michel El Hage ChahineNguyêt-Thanh Ha-Duong
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Jan 18, 2017·Biological Chemistry·Stephanie RockfieldMeera Nanjundan
Oct 3, 2017·Metallomics : Integrated Biometal Science·H AbdizadehB Dedeoglu
Dec 30, 2014·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Guinevere MathiesEdgar J J Groenen
Aug 31, 2020·Redox Biology·Ting Chean KhooAlexander Khmaladze
Jul 28, 2021·Journal of Inorganic Biochemistry·Kyle C EdwardsJohn B Vincent
Apr 12, 2019·ACS Chemical Biology·Aviva Levina, Peter A Lay
Aug 25, 2017·The Journal of Physical Chemistry. B·Sandeep KumarRajesh Kumar
Sep 27, 2012·Journal of Inorganic Biochemistry·Ashley N SteereAnne B Mason

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