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| | ==A mutant human Prolactin receptor antagonist H30A in complex with the extracellular domain of the human prolactin receptor== | | ==A mutant human Prolactin receptor antagonist H30A in complex with the extracellular domain of the human prolactin receptor== |
| - | <StructureSection load='3n0p' size='340' side='right' caption='[[3n0p]], [[Resolution|resolution]] 2.10Å' scene=''> | + | <StructureSection load='3n0p' size='340' side='right'caption='[[3n0p]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3n0p]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N0P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N0P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3n0p]] 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=3N0P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N0P FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3mzg|3mzg]], [[3n06|3n06]], [[3ncb|3ncb]], [[3ncc|3ncc]], [[3nce|3nce]], [[3ncf|3ncf]]</td></tr> | + | <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=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hPRL, PRL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), hPRLr, PRLR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3n0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n0p OCA], [https://pdbe.org/3n0p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n0p RCSB], [https://www.ebi.ac.uk/pdbsum/3n0p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n0p ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3n0p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n0p OCA], [http://pdbe.org/3n0p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3n0p RCSB], [http://www.ebi.ac.uk/pdbsum/3n0p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3n0p ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PRL_HUMAN PRL_HUMAN]] Prolactin acts primarily on the mammary gland by promoting lactation. [[http://www.uniprot.org/uniprot/PRLR_HUMAN PRLR_HUMAN]] This is a receptor for the anterior pituitary hormone prolactin (PRL). Isoform 4 is unable to transduce prolactin signaling. Isoform 6 is unable to transduce prolactin signaling.<ref>PMID:12580759</ref> | + | [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]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Chayen, N E]] | + | [[Category: Large Structures]] |
| - | [[Category: Hodsdon, M E]] | + | [[Category: Chayen NE]] |
| - | [[Category: Keeler, C]] | + | [[Category: Hodsdon ME]] |
| - | [[Category: Kulkarni, M V]] | + | [[Category: Keeler C]] |
| - | [[Category: Lolis, E J]] | + | [[Category: Kulkarni MV]] |
| - | [[Category: Murphy, J W]] | + | [[Category: Lolis EJ]] |
| - | [[Category: Myszka, D G]] | + | [[Category: Murphy JW]] |
| - | [[Category: Tettamanzi, M C]] | + | [[Category: Myszka DG]] |
| - | [[Category: Hematopoietic cytokine]]
| + | [[Category: Tettamanzi MC]] |
| - | [[Category: Hormone-hormone receptor complex]]
| + | |
| - | [[Category: Ph dependence]]
| + | |
| Structural highlights
Function
PRL_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 PubMed
Human 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 Also
References
- ↑ Kulkarni MV, Tettamanzi MC, Murphy JW, Keeler C, Myszka DG, Chayen NE, Lolis EJ, Hodsdon ME. Two independent histidines, one in human prolactin and one in its receptor, are critical for pH dependent receptor recognition and activation. J Biol Chem. 2010 Sep 30. PMID:20889499 doi:10.1074/jbc.M110.172072
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