|
|
| (One intermediate revision not shown.) |
| Line 3: |
Line 3: |
| | <StructureSection load='1n84' size='340' side='right'caption='[[1n84]], [[Resolution|resolution]] 2.05Å' scene=''> | | <StructureSection load='1n84' size='340' side='right'caption='[[1n84]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1n84]] is a 1 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=1N84 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1N84 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1n84]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N84 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1N84 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1n7w|1n7w]], [[1n7x|1n7x]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=FE:FE+(III)+ION'>FE</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">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'>[https://proteopedia.org/fgij/fg.htm?mol=1n84 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n84 OCA], [https://pdbe.org/1n84 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1n84 RCSB], [https://www.ebi.ac.uk/pdbsum/1n84 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1n84 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1n84 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n84 OCA], [http://pdbe.org/1n84 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1n84 RCSB], [http://www.ebi.ac.uk/pdbsum/1n84 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1n84 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TRFE_HUMAN TRFE_HUMAN]] Defects in TF are the cause of atransferrinemia (ATRAF) [MIM:[http://omim.org/entry/209300 209300]]. Atransferrinemia is rare autosomal recessive disorder characterized by iron overload and hypochromic anemia.<ref>PMID:11110675</ref> <ref>PMID:15466165</ref> | + | [https://www.uniprot.org/uniprot/TRFE_HUMAN TRFE_HUMAN] Defects in TF are the cause of atransferrinemia (ATRAF) [MIM:[https://omim.org/entry/209300 209300]. Atransferrinemia is rare autosomal recessive disorder characterized by iron overload and hypochromic anemia.<ref>PMID:11110675</ref> <ref>PMID:15466165</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TRFE_HUMAN 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. | + | [https://www.uniprot.org/uniprot/TRFE_HUMAN 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. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 18: |
Line 17: |
| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n8/1n84_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n8/1n84_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| Line 39: |
Line 38: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Adams, T E]] | + | [[Category: Adams TE]] |
| - | [[Category: Briggs, S K]] | + | [[Category: Briggs SK]] |
| - | [[Category: Everse, S J]] | + | [[Category: Everse SJ]] |
| - | [[Category: Halbrooks, P J]] | + | [[Category: Halbrooks PJ]] |
| - | [[Category: He, Q Y]] | + | [[Category: He QY]] |
| - | [[Category: Macgillivray, R T]] | + | [[Category: Macgillivray RT]] |
| - | [[Category: Mason, A B]] | + | [[Category: Mason AB]] |
| - | [[Category: Smith, V C]] | + | [[Category: Smith VC]] |
| - | [[Category: Iron transport]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
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
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.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Human serum transferrin (hTF) is a bilobal iron-binding and transport protein that carries iron in the blood stream for delivery to cells by a pH-dependent mechanism. Two iron atoms are held tightly in two deep clefts by coordination to four amino acid residues in each cleft (two tyrosines, a histidine, and an aspartic acid) and two oxygen atoms from the "synergistic" carbonate anion. Other residues in the binding pocket, not directly coordinated to iron, also play critical roles in iron uptake and release through hydrogen bonding to the liganding residues. The original crystal structures of the iron-loaded N-lobe of hTF (pH 5.75 and 6.2) revealed that the synergistic carbonate is stabilized by interaction with Arg-124 and that both the arginine and the carbonate adopt two conformations (MacGillivray, R. T. A., Moore, S. A., Chen, J., Anderson, B. F., Baker, H., Luo, Y. G., Bewley, M., Smith, C. A., Murphy, M. E., Wang, Y., Mason, A. B., Woodworth, R. C., Brayer, G. D., and Baker, E. N. (1998) Biochemistry 37, 7919-7928). In the present study, we show that the two conformations are also found for a structure at pH 7.7, indicating that this finding was not strictly a function of pH. We also provide structures for two single point mutants (Y45E and L66W) designed to force Arg-124 to adopt each of the previously observed conformations. The structures of each mutant show that this goal was accomplished, and functional studies confirm the hypothesis that access to the synergistic anion dictates the rate of iron release. These studies highlight the importance of the arginine/carbonate movement in the mechanism of iron release in the N-lobe of hTF. Access to the carbonate via a water channel allows entry of protons and anions, enabling the attack on the iron.
The position of arginine 124 controls the rate of iron release from the N-lobe of human serum transferrin. A structural study.,Adams TE, Mason AB, He QY, Halbrooks PJ, Briggs SK, Smith VC, MacGillivray RT, Everse SJ J Biol Chem. 2003 Feb 21;278(8):6027-33. Epub 2002 Nov 27. PMID:12458193[3]
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
- ↑ Adams TE, Mason AB, He QY, Halbrooks PJ, Briggs SK, Smith VC, MacGillivray RT, Everse SJ. The position of arginine 124 controls the rate of iron release from the N-lobe of human serum transferrin. A structural study. J Biol Chem. 2003 Feb 21;278(8):6027-33. Epub 2002 Nov 27. PMID:12458193 doi:10.1074/jbc.M210349200
|
