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4k71
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of a high affinity Human Serum Albumin variant bound to the Neonatal Fc Receptor== | |
| + | <StructureSection load='4k71' size='340' side='right'caption='[[4k71]], [[Resolution|resolution]] 2.40Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4k71]] is a 6 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=4K71 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4K71 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4k71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k71 OCA], [https://pdbe.org/4k71 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k71 RCSB], [https://www.ebi.ac.uk/pdbsum/4k71 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k71 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/ALBU_HUMAN ALBU_HUMAN] Defects in ALB are a cause of familial dysalbuminemic hyperthyroxinemia (FDH) [MIM:[https://omim.org/entry/103600 103600]. FDH is a form of euthyroid hyperthyroxinemia that is due to increased affinity of ALB for T(4). It is the most common cause of inherited euthyroid hyperthyroxinemia in Caucasian population.<ref>PMID:8048949</ref> <ref>PMID:7852505</ref> <ref>PMID:9329347</ref> <ref>PMID:9589637</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ALBU_HUMAN ALBU_HUMAN] Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.<ref>PMID:19021548</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The long circulating half-life of serum albumin, the most abundant protein in mammalian plasma, derives from pH-dependent endosomal salvage from degradation, mediated by the neonatal Fc receptor (FcRn). Using yeast display, we identified human serum albumin (HSA) variants with increased affinity for human FcRn at endosomal pH, enabling us to solve the crystal structure of a variant HSA/FcRn complex. We find an extensive, primarily hydrophobic interface stabilized by hydrogen-bonding networks involving protonated histidines internal to each protein. The interface features two key FcRn tryptophan side chains inserting into deep hydrophobic pockets on HSA that overlap albumin ligand binding sites. We find that fatty acids (FAs) compete with FcRn, revealing a clash between ligand binding and recycling, and that our high-affinity HSA variants have significantly increased circulating half-lives in mice and monkeys. These observations open the way for the creation of biotherapeutics with significantly improved pharmacokinetics. | ||
| - | + | Crystal structure of an HSA/FcRn complex reveals recycling by competitive mimicry of HSA ligands at a pH-dependent hydrophobic interface.,Schmidt MM, Townson SA, Andreucci AJ, King BM, Schirmer EB, Murillo AJ, Dombrowski C, Tisdale AW, Lowden PA, Masci AL, Kovalchin JT, Erbe DV, Wittrup KD, Furfine ES, Barnes TM Structure. 2013 Nov 5;21(11):1966-78. doi: 10.1016/j.str.2013.08.022. Epub 2013, Oct 10. PMID:24120761<ref>PMID:24120761</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4k71" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Albumin 3D structures|Albumin 3D structures]] | ||
| + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Andreucci A]] | ||
| + | [[Category: Barnes TM]] | ||
| + | [[Category: Dombrowski C]] | ||
| + | [[Category: Erbe DV]] | ||
| + | [[Category: Furfine ES]] | ||
| + | [[Category: King B]] | ||
| + | [[Category: Kovalchin JT]] | ||
| + | [[Category: Masci A]] | ||
| + | [[Category: Murillo A]] | ||
| + | [[Category: Schirmer EB]] | ||
| + | [[Category: Schmidt MM]] | ||
| + | [[Category: Townson SA]] | ||
Current revision
Crystal structure of a high affinity Human Serum Albumin variant bound to the Neonatal Fc Receptor
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Categories: Homo sapiens | Large Structures | Andreucci A | Barnes TM | Dombrowski C | Erbe DV | Furfine ES | King B | Kovalchin JT | Masci A | Murillo A | Schirmer EB | Schmidt MM | Townson SA
