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==A human Prolactin receptor antagonist in complex with the mutant extracellular domain H188A of the human prolactin receptor== | ==A human Prolactin receptor antagonist in complex with the mutant extracellular domain H188A of the human prolactin receptor== | ||
<StructureSection load='3ncc' size='340' side='right' caption='[[3ncc]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='3ncc' size='340' side='right'caption='[[3ncc]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3ncc]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3ncc]] 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=3NCC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NCC FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=3ncc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ncc OCA], [https://pdbe.org/3ncc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ncc RCSB], [https://www.ebi.ac.uk/pdbsum/3ncc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ncc ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/PRL_HUMAN PRL_HUMAN] Prolactin acts primarily on the mammary gland by promoting lactation. | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nc/3ncc_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nc/3ncc_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
| Line 30: | Line 29: | ||
</div> | </div> | ||
<div class="pdbe-citations 3ncc" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 3ncc" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Prolactin|Prolactin]] | |||
*[[Prolactin receptor|Prolactin receptor]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Chayen | [[Category: Large Structures]] | ||
[[Category: Hodsdon | [[Category: Chayen NE]] | ||
[[Category: Keeler | [[Category: Hodsdon ME]] | ||
[[Category: Kulkarni | [[Category: Keeler C]] | ||
[[Category: Lolis | [[Category: Kulkarni MV]] | ||
[[Category: Murphy | [[Category: Lolis EJ]] | ||
[[Category: Myszka | [[Category: Murphy JW]] | ||
[[Category: Tettamanzi | [[Category: Myszka DG]] | ||
[[Category: Tettamanzi MC]] | |||
Revision as of 12:12, 6 September 2023
A human Prolactin receptor antagonist in complex with the mutant extracellular domain H188A of the human prolactin receptorA human Prolactin receptor antagonist in complex with the mutant extracellular domain H188A of the human prolactin receptor
Structural highlights
FunctionPRL_HUMAN Prolactin acts primarily on the mammary gland by promoting lactation. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHuman prolactin (hPRL), a member of the family of hematopoietic cytokines, functions as both an endocrine hormone and autocrine/paracrine growth factor. We have previously demonstrated that recognition of the hPRL receptor (hPRLr) depends strongly on solution acidity over the physiologic range from pH 6 &- 8. The hPRL-receptor binding interface contains four histidines, whose protonation is hypothesized to regulate pH-dependent receptor recognition. Here, we systematically dissect its molecular origin by characterizing the consequences of His to Ala mutations on pH-dependent receptor-binding kinetics, site-specific histidine protonation, and high resolution structures of the intermolecular interface. Thermodynamic modeling of the pH dependence to receptor-binding affinity reveals large changes in site-specific protonation constants for a majority of interface histidines upon complexation. Removal of individual His imidazoles reduces these perturbations in protonation constants, which is most likely explained by the introduction of solvent-filled, buried cavities in the crystallographic structures without inducing significant conformational rearrangements. Two independent histidines, one in human prolactin and one in its receptor, are critical for pH dependent receptor recognition and activation.,Kulkarni MV, Tettamanzi MC, Murphy JW, Keeler C, Myszka DG, Chayen NE, Lolis EJ, Hodsdon ME J Biol Chem. 2010 Sep 30. PMID:20889499[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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