View source for 2riv


==Crystal structure of the reactive loop cleaved human Thyroxine Binding Globulin==
<StructureSection load='2riv' size='340' side='right'caption='[[2riv]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2riv]] is a 2 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=2RIV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RIV 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]] 1.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <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=2riv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2riv OCA], [https://pdbe.org/2riv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2riv RCSB], [https://www.ebi.ac.uk/pdbsum/2riv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2riv ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/THBG_HUMAN THBG_HUMAN] Defects in SERPINA7 are a cause of thyroxine-binding globulin deficiency (TBG deficiency) [MIM:[https://omim.org/entry/314200 314200]. Mutations in the SERPINA7 gene can result as a whole spectrum of deficiencies, characterized by either reduced or increased TBG levels in the serum. Patients show, respectively, reduced or elevated protein-bound iodine but are euthyroid.
== Function ==
[https://www.uniprot.org/uniprot/THBG_HUMAN THBG_HUMAN] Major thyroid hormone transport protein in serum.
== 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/ri/2riv_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2riv ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The release of hormones from thyroxine-binding globulin (TBG) and corticosteroid-binding globulin (CBG) is regulated by movement of the reactive-center loop in-and-out of the beta-sheet A of the molecule. To investigate how these changes are transmitted to the hormone-binding site we developed a sensitive assay using a synthesized thyroxine-fluorophore and solved the crystal structures of reactive-loop cleaved TBG together with its complexes with thyroxine, the thyroxine-fluorophores, furosemide, and mefenamic acid. Cleavage of the reactive-loop results in its complete insertion into the beta-sheet A and a substantial but incomplete decrease in binding affinity in both TBG and CBG. We show here that the direct interaction between residue P14 of the reactive loop and Tyr241 of the hormone binding site contributes to thyroxine binding and release following reactive loop insertion. However a much larger effect occurs allosterically due to stretching of the connecting-loop to the top of the D helix (hD) as confirmed in TBG with shortening of the loop by 3-residues making it insensitive to the S-to-R transition. The transmission of the changes in the hD-loop to the binding pocket is seen to involve coherent movements in the s2/3B loop linked to the hD-loop by Lys243 which is in turn linked to the s4/5B loop, flanking the thyroxine binding site, by Arg378. Overall the coordinated movements of the reactive-loop, hD and the hormone binding site, allow the allosteric regulation of hormone-release, as with the modulation demonstrated here in response to changes in temperature.

Allosteric modulation of hormone release from thyroxine and corticosteroid binding-globulins.,Qi X, Loiseau F, Chan WL, Yan Y, Wei Z, Milroy LG, Myers RM, Ley SV, Read RJ, Carrell RW, Zhou A J Biol Chem. 2011 Feb 16. PMID:21325280<ref>PMID:21325280</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2riv" style="background-color:#fffaf0;"></div>

==See Also==
*[[Serpin 3D structures|Serpin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Carrell RW]]
[[Category: Read RJ]]
[[Category: Stanley PLD]]
[[Category: Stein PE]]
[[Category: Wei Z]]
[[Category: Zhou A]]