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| | ==Complex between transferrin receptor 1 and transferrin with iron in the N-Lobe, cryocooled 1== | | ==Complex between transferrin receptor 1 and transferrin with iron in the N-Lobe, cryocooled 1== |
| | <StructureSection load='3s9m' size='340' side='right' caption='[[3s9m]], [[Resolution|resolution]] 3.32Å' scene=''> | | <StructureSection load='3s9m' size='340' side='right' caption='[[3s9m]], [[Resolution|resolution]] 3.32Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3s9m]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S9M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3S9M FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3s9m]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S9M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3S9M FirstGlance]. <br> |
| | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1cx8|1cx8]], [[1a8e|1a8e]], [[2hau|2hau]], [[3s9l|3s9l]], [[3s9n|3s9n]]</td></tr> | | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1cx8|1cx8]], [[1a8e|1a8e]], [[2hau|2hau]], [[3s9l|3s9l]], [[3s9n|3s9n]]</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TFR1, TFRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), PRO1400, TF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TFR1, TFRC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PRO1400, TF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3s9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s9m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3s9m RCSB], [http://www.ebi.ac.uk/pdbsum/3s9m PDBsum]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3s9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s9m OCA], [http://pdbe.org/3s9m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3s9m RCSB], [http://www.ebi.ac.uk/pdbsum/3s9m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3s9m ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3s9m" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Homo sapiens]] | + | [[Category: Human]] |
| | [[Category: Eckenroth, B E]] | | [[Category: Eckenroth, B E]] |
| | [[Category: Everse, S J]] | | [[Category: Everse, S J]] |
| 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.[1] [2]
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.[3] [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[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Beutler E, Gelbart T, Lee P, Trevino R, Fernandez MA, Fairbanks VF. Molecular characterization of a case of atransferrinemia. Blood. 2000 Dec 15;96(13):4071-4. PMID:11110675
- ↑ Knisely AS, Gelbart T, Beutler E. Molecular characterization of a third case of human atransferrinemia. Blood. 2004 Oct 15;104(8):2607. PMID:15466165 doi:10.1182/blood-2004-05-1751
- ↑ Rothenberger S, Iacopetta BJ, Kuhn LC. Endocytosis of the transferrin receptor requires the cytoplasmic domain but not its phosphorylation site. Cell. 1987 May 8;49(3):423-31. PMID:3568132
- ↑ Eckenroth BE, Steere AN, Chasteen ND, Everse SJ, Mason AB. How the binding of human transferrin primes the transferrin receptor potentiating iron release at endosomal pH. Proc Natl Acad Sci U S A. 2011 Jul 25. PMID:21788477 doi:10.1073/pnas.1105786108
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