2vq3: Difference between revisions

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[[Image:2vq3.~~jpg~~|left|200px]]

[[Image:2vq3.png|left|200px]]

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~~'''~~CRYSTAL STRUCTURE OF THE MEMBRANE PROXIMAL OXIDOREDUCTASE DOMAIN OF HUMAN STEAP3, THE DOMINANT FERRIC REDUCTASE OF THE ERYTHROID TRANSFERRIN CYCLE~~'''~~

===CRYSTAL STRUCTURE OF THE MEMBRANE PROXIMAL OXIDOREDUCTASE DOMAIN OF HUMAN STEAP3, THE DOMINANT FERRIC REDUCTASE OF THE ERYTHROID TRANSFERRIN CYCLE===

~~==Overview==~~

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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.

The line below this paragraph, {{ABSTRACT_PUBMED_18495927}}, adds the Publication Abstract to the page

(as it appears on PubMed at http://www.pubmed.gov), where 18495927 is the PubMed ID number.

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==About this Structure==

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==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]

Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells., Ohgami RS, Campagna DR, Greer EL, Antiochos B, McDonald A, Chen J, Sharp JJ, Fujiwara Y, Barker JE, Fleming MD, Nat Genet. 2005 Nov;37(11):1264-9. Epub 2005 Oct 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16227996 16227996]

nm1054: a spontaneous, recessive, hypochromic, microcytic anemia mutation in the mouse., Ohgami RS, Campagna DR, Antiochos B, Wood EB, Sharp JJ, Barker JE, Fleming MD, Blood. 2005 Nov 15;106(10):3625-31. Epub 2005 Jun 30. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15994289 15994289]

[[Category: Homo sapiens]]

[[Category: Single protein]]

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[[Category: Transmembrane]]

[[Category: Transport]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed Jun 4 09~~:59:49 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 18:51:01 2008''

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-[[Image:2vq3.jpg|left|200px]]
+{{Seed}}
+[[Image:2vq3.png|left|200px]]
 <!--
@@ Line 9: / Line 10: @@
 {{STRUCTURE_2vq3|  PDB=2vq3  |  SCENE=  }}
-'''CRYSTAL STRUCTURE OF THE MEMBRANE PROXIMAL OXIDOREDUCTASE DOMAIN OF HUMAN STEAP3, THE DOMINANT FERRIC REDUCTASE OF THE ERYTHROID TRANSFERRIN CYCLE'''
+===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.
+The line below this paragraph, {{ABSTRACT_PUBMED_18495927}}, adds the Publication Abstract to the page
+(as it appears on PubMed at http://www.pubmed.gov), where 18495927 is the PubMed ID number.
+-->
+{{ABSTRACT_PUBMED_18495927}}
 ==About this Structure==
@@ Line 20: / Line 24: @@
 ==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]
+Identification of a ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells., Ohgami RS, Campagna DR, Greer EL, Antiochos B, McDonald A, Chen J, Sharp JJ, Fujiwara Y, Barker JE, Fleming MD, Nat Genet. 2005 Nov;37(11):1264-9. Epub 2005 Oct 16. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16227996 16227996]
+nm1054: a spontaneous, recessive, hypochromic, microcytic anemia mutation in the mouse., Ohgami RS, Campagna DR, Antiochos B, Wood EB, Sharp JJ, Barker JE, Fleming MD, Blood. 2005 Nov 15;106(10):3625-31. Epub 2005 Jun 30. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15994289 15994289]
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
@@ Line 58: / Line 66: @@
 [[Category: Transmembrane]]
 [[Category: Transport]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun  4 09:59:49 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 18:51:01 2008''