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4hgm

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Revision as of 09:33, 5 February 2020

Shark IgNAR Variable Domain

Structural highlights

4hgm is a 2 chain structure with sequence from Human and Squac. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4hgk
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ALBU_HUMAN] Defects in ALB are a cause of familial dysalbuminemic hyperthyroxinemia (FDH) [MIM: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.^[1] ^[2] ^[3] ^[4]

Function

[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.^[5]

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Sunthornthepvarakul T, Angkeow P, Weiss RE, Hayashi Y, Refetoff S. An identical missense mutation in the albumin gene results in familial dysalbuminemic hyperthyroxinemia in 8 unrelated families. Biochem Biophys Res Commun. 1994 Jul 29;202(2):781-7. PMID:8048949
↑ Rushbrook JI, Becker E, Schussler GC, Divino CM. Identification of a human serum albumin species associated with familial dysalbuminemic hyperthyroxinemia. J Clin Endocrinol Metab. 1995 Feb;80(2):461-7. PMID:7852505
↑ Wada N, Chiba H, Shimizu C, Kijima H, Kubo M, Koike T. A novel missense mutation in codon 218 of the albumin gene in a distinct phenotype of familial dysalbuminemic hyperthyroxinemia in a Japanese kindred. J Clin Endocrinol Metab. 1997 Oct;82(10):3246-50. PMID:9329347
↑ Sunthornthepvarakul T, Likitmaskul S, Ngowngarmratana S, Angsusingha K, Kitvitayasak S, Scherberg NH, Refetoff S. Familial dysalbuminemic hypertriiodothyroninemia: a new, dominantly inherited albumin defect. J Clin Endocrinol Metab. 1998 May;83(5):1448-54. PMID:9589637
↑ Lu J, Stewart AJ, Sadler PJ, Pinheiro TJ, Blindauer CA. Albumin as a zinc carrier: properties of its high-affinity zinc-binding site. Biochem Soc Trans. 2008 Dec;36(Pt 6):1317-21. doi: 10.1042/BST0361317. PMID:19021548 doi:10.1042/BST0361317
↑ 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. Atypical Antigen Recognition Mode of a Shark IgNAR Variable Domain Characterized by Humanization and Structural Analysis. J Biol Chem. 2013 Apr 30. PMID:23632026 doi:10.1074/jbc.M112.435289

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4hgm"

@@ Line 1: / Line 1: @@
 ==Shark IgNAR Variable Domain==
-<StructureSection load='4hgm' size='340' side='right' caption='[[4hgm]], [[Resolution|resolution]] 2.34&Aring;' scene=''>
+<StructureSection load='4hgm' size='340' side='right'caption='[[4hgm]], [[Resolution|resolution]] 2.34&Aring;' scene=''>
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4hgm]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Squac Squac]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HGM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HGM FirstGlance]. <br>
@@ Line 21: / Line 21: @@
 </div>
 <div class="pdbe-citations 4hgm" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Albumin 3D structures|Albumin 3D structures]]
 == References ==
 <references/>
@@ Line 26: / Line 29: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Squac]]
 [[Category: King, D]]

4hgm

From Proteopedia

Revision as of 09:33, 5 February 2020

Shark IgNAR Variable Domain

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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