View source for 2o84


==Crystal structure of K206E mutant of N-lobe human transferrin==
<StructureSection load='2o84' size='340' side='right'caption='[[2o84]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2o84]] 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=2O84 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2O84 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</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>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></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=2o84 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o84 OCA], [https://pdbe.org/2o84 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2o84 RCSB], [https://www.ebi.ac.uk/pdbsum/2o84 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2o84 ProSAT]</span></td></tr>
</table>
== Disease ==
[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 ==
[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 ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/o8/2o84_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2o84 ConSurf].
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== Publication Abstract from PubMed ==
Iron uptake by humans depends on the ability of the serum protein transferrin (Tf) to bind iron as Fe(3+) with high affinity but reversibly. Iron release into cells occurs through receptor-mediated endocytosis, aided by the lower endosomal pH of about 5.5. The protonation of a hydrogen-bonded pair of lysines, Lys206 and Lys296, adjacent to the N-lobe iron site of Tf has been proposed to create a repulsive interaction that stimulates domain opening and iron release. The crystal structures of two mutants, K206E (in which Lys206 is mutated to Glu) and K206E/K296E (in which both lysines are mutated to Glu), have been determined. The K206E structure (2.6 A resolution; R = 0.213, R(free) = 0.269) shows that a salt bridge is formed between Glu206 and Lys296, thus explaining the drastically slower iron release by this mutant. The K206E/K296E double-mutant structure (2.8 A resolution; R = 0.232, R(free) = 0.259) shows that the Glu296 side chain moves away from Glu206, easing any repulsive interaction and instead interacting with the iron ligand His249. The evident conformational flexibility is consistent with an alternative model for the operation of the dilysine pair in iron release in which it facilitates concerted proton transfer to the tyrosine ligand Tyr188 as one step in the weakening of iron binding.

Structures of two mutants that probe the role in iron release of the dilysine pair in the N-lobe of human transferrin.,Baker HM, Nurizzo D, Mason AB, Baker EN Acta Crystallogr D Biol Crystallogr. 2007 Mar;63(Pt 3):408-14. Epub 2007, Feb 21. PMID:17327678<ref>PMID:17327678</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Transferrin 3D structures|Transferrin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Baker EN]]
[[Category: Baker HM]]
[[Category: Mason AB]]
[[Category: Nurizzo D]]