3s9m

Complex between transferrin receptor 1 and transferrin with iron in the N-Lobe, cryocooled 1Complex between transferrin receptor 1 and transferrin with iron in the N-Lobe, cryocooled 1

Structural highlights 3s9m is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , , , Related: 1cx8, 1a8e, 2hau, 3s9l, 3s9n Gene: TFR1, TFRC (HUMAN), PRO1400, TF (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [TRFE_HUMAN] Defects in TF are the cause of atransferrinemia (ATRAF) [MIM:209300]. Atransferrinemia is rare autosomal recessive disorder characterized by iron overload and hypochromic anemia. Function [TFR1_HUMAN] Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes. Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). A second ligand, the heditary hemochromatosis protein HFE, competes for binding with transferrin for an overlapping C-terminal binding site. [TRFE_HUMAN] Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation. Publication Abstract from PubMed Delivery of iron to cells requires binding of two iron-containing human transferrin (hTF) molecules to the specific homodimeric transferrin receptor (TFR) on the cell surface. Through receptor-mediated endocytosis involving lower pH, salt, and an unidentified chelator, iron is rapidly released from hTF within the endosome. The crystal structure of a monoferric N-lobe hTF/TFR complex (3.22-A resolution) features two binding motifs in the N lobe and one in the C lobe of hTF. Binding of Fe(N)hTF induces global and site-specific conformational changes within the TFR ectodomain. Specifically, movements at the TFR dimer interface appear to prime the TFR to undergo pH-induced movements that alter the hTF/TFR interaction. Iron release from each lobe then occurs by distinctly different mechanisms: Binding of His349 to the TFR (strengthened by protonation at low pH) controls iron release from the C lobe, whereas displacement of one N-lobe binding motif, in concert with the action of the dilysine trigger, elicits iron release from the N lobe. One binding motif in each lobe remains attached to the same alpha-helix in the TFR throughout the endocytic cycle. Collectively, the structure elucidates how the TFR accelerates iron release from the C lobe, slows it from the N lobe, and stabilizes binding of apohTF for return to the cell surface. Importantly, this structure provides new targets for mutagenesis studies to further understand and define this system. How the binding of human transferrin primes the transferrin receptor potentiating iron release at endosomal pH.,Eckenroth BE, Steere AN, Chasteen ND, Everse SJ, Mason AB Proc Natl Acad Sci U S A. 2011 Jul 25. PMID:21788477 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transferrin 3D structures Transferrin receptor Transferrin-binding protein

spinqualitylabelsall models 3s9m, resolution 3.32Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image