2VQ3

Crystal Structure of the Membrane Proximal Oxidoreductase Domain of Human Steap3, the Dominant Ferric Reductase of the Erythroid Transferrin Cycle

Summary for 2VQ3

• Entry DOI: 10.2210/pdb2vq3/pdb
• Related: 2VNS
• Descriptor: METALLOREDUCTASE STEAP3, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, CITRIC ACID, ... (4 entities in total)
• Functional Keywords: metal-binding, transmembrane, rossmann fold, transport, cell cycle, transferrin, flavoprotein, alternative splicing, transferrin receptor, ferrireductase, ferric-reductase, iron transport, phosphoprotein, oxidoreductase, steap3, copper, membrane, endosome, apoptosis, tf, nad, tfr, fad, fno, nadp, tfr1, iron, steap, polymorphism, glycoprotein, ion transport, dinucleotide-binding domain
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Endosome membrane; Multi-pass membrane protein (By similarity): Q658P3
• Total number of polymer chains: 2
• Total formula weight: 48310.29

Authors

Sendamarai, A.K.,Ohgami, R.S.,Fleming, M.D.,Lawrence, C.M. (deposition date: 2008-03-10, release date: 2008-05-06, Last modification date: 2024-01-31)

Primary citation

Sendamarai, A.K.,Ohgami, R.S.,Fleming, M.D.,Lawrence, C.M.
Structure of the Membrane Proximal Oxidoreductase Domain of Human Steap3, the Dominant Ferrireductase of the Erythroid Transferrin Cycle
Proc.Natl.Acad.Sci.USA, 105:7410-, 2008

PubMed Abstract: 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.

PubMed: 18495927
DOI: 10.1073/PNAS.0801318105

Experimental method

X-RAY DIFFRACTION (2 Å)