View source for 4hgk


==Shark IgNAR variable domain==
<StructureSection load='4hgk' size='340' side='right'caption='[[4hgk]], [[Resolution|resolution]] 3.04&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4hgk]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Squalus_acanthias Squalus acanthias]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HGK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HGK 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]] 3.04&#8491;</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=4hgk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hgk OCA], [https://pdbe.org/4hgk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hgk RCSB], [https://www.ebi.ac.uk/pdbsum/4hgk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hgk 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> 
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== Publication Abstract from PubMed ==
The immunoglobulin new antigen receptors (IgNARs) are a class of Ig-like molecules of the shark immune system that exist as heavy chain-only homodimers and bind antigens by their single-domain variable regions (V-NARs). Following shark immunization and/or in vitro selection, V-NARs can be generated as soluble, stable and specific high-affinity monomeric binding proteins of ~12 kDa. We have previously isolated a V-NAR from an immunized spiny dogfish shark, named E06, which binds specifically and with high affinity to human, mouse and rat serum albumins. Humanization of E06 was carried out by converting over 60% of non-CDR residues to that of a human germline Vkappa1 sequence, DPK9. The resulting huE06 molecules have largely retained the specificity and affinity of antigen binding of the parental V-NAR. Crystal structures of the shark E06 and its humanized variant (huE06 v1.1), in complex with HSA, were determined at 3A and 2.3A resolution, respectively. The huE06 v1.1 molecule retained all but one amino acid residues involved in the binding site for HSA. Structural analysis of these V-NARs has revealed an unusual variable domain-antigen interaction. E06 interacts with HSA in an atypical mode that utilizes extensive framework contacts in addition to CDRs, that has not been previously seen in V-NARs. On the basis of the structure, the roles of various elements of the molecule are described with respect to antigen binding and V-NAR stability. This information broadens the general understanding of antigen recognition and provides a framework for further design and humanization of shark IgNARs.

Atypical Antigen Recognition Mode of a Shark IgNAR Variable Domain Characterized by Humanization and Structural Analysis.,Kovalenko OV, Olland A, Piche-Nicholas N, Godbole A, King D, Svenson K, Calabro V, Muller MR, Barelle CJ, Somers W, Gill DS, Mosyak L, Tchistiakova L J Biol Chem. 2013 Apr 30. PMID:23632026<ref>PMID:23632026</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4hgk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Albumin 3D structures|Albumin 3D structures]]
*[[Antibody 3D structures|Antibody 3D structures]]
*[[3D structures of non-human antibody|3D structures of non-human antibody]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Squalus acanthias]]
[[Category: King D]]
[[Category: Kovalenko OV]]
[[Category: Olland AO]]
[[Category: Svenson K]]