2vq3
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The | + | The daily production of 200 billion erythrocytes requires 20 mg of iron, accounting for nearly 80% of the iron demand in humans. Thus, erythroid precursor cells possess an efficient mechanism for iron uptake in which iron loaded transferrin (Tf) binds to the transferrin receptor (TfR) at the cell surface. The Tf:TfR complex then enters the endosome via receptor-mediated endocytosis. Upon endosomal acidification, iron is released from Tf, reduced to Fe(2+) by Steap3, and transported across the endosomal membrane by divalent metal iron transporter 1. Steap3, the major ferrireductase in erythrocyte endosomes, is a member of a unique family of reductases. Steap3 is comprised of an N-terminal cytosolic oxidoreductase domain and a C-terminal heme-containing transmembrane domain. Cytosolic NADPH and a flavin are predicted cofactors, but the NADPH/flavin binding domain differs significantly from those in other eukaryotic reductases. Instead, Steap3 shows remarkable, although limited homology to FNO, an archaeal oxidoreductase. We have determined the crystal structure of the human Steap3 oxidoreductase domain in the absence and presence of NADPH. The structure reveals an FNO-like domain with an unexpected dimer interface and substrate binding sites that are well positioned to direct electron transfer from the cytosol to a heme moiety predicted to be fixed within the transmembrane domain. Here, we discuss possible gating mechanisms for electron transfer across the endosomal membrane. |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | + | Structure of the membrane proximal oxidoreductase domain of human Steap3, the dominant ferrireductase of the erythroid transferrin cycle., Sendamarai AK, Ohgami RS, Fleming MD, Lawrence CM, Proc Natl Acad Sci U S A. 2008 May 27;105(21):7410-5. Epub 2008 May 21. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18495927 18495927] | |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Transmembrane]] | [[Category: Transmembrane]] | ||
[[Category: Transport]] | [[Category: Transport]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 4 09:59:49 2008'' |
Revision as of 06:59, 4 June 2008
CRYSTAL STRUCTURE OF THE MEMBRANE PROXIMAL OXIDOREDUCTASE DOMAIN OF HUMAN STEAP3, THE DOMINANT FERRIC REDUCTASE OF THE ERYTHROID TRANSFERRIN CYCLE
Overview
The daily production of 200 billion erythrocytes requires 20 mg of iron, accounting for nearly 80% of the iron demand in humans. Thus, erythroid precursor cells possess an efficient mechanism for iron uptake in which iron loaded transferrin (Tf) binds to the transferrin receptor (TfR) at the cell surface. The Tf:TfR complex then enters the endosome via receptor-mediated endocytosis. Upon endosomal acidification, iron is released from Tf, reduced to Fe(2+) by Steap3, and transported across the endosomal membrane by divalent metal iron transporter 1. Steap3, the major ferrireductase in erythrocyte endosomes, is a member of a unique family of reductases. Steap3 is comprised of an N-terminal cytosolic oxidoreductase domain and a C-terminal heme-containing transmembrane domain. Cytosolic NADPH and a flavin are predicted cofactors, but the NADPH/flavin binding domain differs significantly from those in other eukaryotic reductases. Instead, Steap3 shows remarkable, although limited homology to FNO, an archaeal oxidoreductase. We have determined the crystal structure of the human Steap3 oxidoreductase domain in the absence and presence of NADPH. The structure reveals an FNO-like domain with an unexpected dimer interface and substrate binding sites that are well positioned to direct electron transfer from the cytosol to a heme moiety predicted to be fixed within the transmembrane domain. Here, we discuss possible gating mechanisms for electron transfer across the endosomal membrane.
About this Structure
2VQ3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of the membrane proximal oxidoreductase domain of human Steap3, the dominant ferrireductase of the erythroid transferrin cycle., Sendamarai AK, Ohgami RS, Fleming MD, Lawrence CM, Proc Natl Acad Sci U S A. 2008 May 27;105(21):7410-5. Epub 2008 May 21. PMID:18495927 Page seeded by OCA on Wed Jun 4 09:59:49 2008
Categories: Homo sapiens | Single protein | Fleming, M D. | Lawrence, C M. | Ohgami, R S. | Sendamarai, A K. | Alternative splicing | Apoptosis | Cell cycle | Copper | Dinucleotide-binding domain | Endosome | Fad | Ferric- reductase | Ferrireductase | Flavoprotein | Fno | Glycoprotein | Ion transport | Iron | Iron transport | Membrane | Metal-binding | Nad | Nadp | Oxidoreductase | Phosphoprotein | Polymorphism | Rossmann fold | Steap | Steap3 | Tf | Tfr | Tfr1 | Transferrin | Transferrin receptor | Transmembrane | Transport
