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| | ==Solution structure of the human prolactin receptor ecd domain d2== | | ==Solution structure of the human prolactin receptor ecd domain d2== |
| - | <StructureSection load='2lfg' size='340' side='right'caption='[[2lfg]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2lfg' size='340' side='right'caption='[[2lfg]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2lfg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LFG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LFG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2lfg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LFG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LFG FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1rw5|1rw5]], [[3ew3|3ew3]], [[3npz|3npz]], [[3d48|3d48]], [[3mzg|3mzg]]</div></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRLR ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2lfg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lfg OCA], [https://pdbe.org/2lfg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lfg RCSB], [https://www.ebi.ac.uk/pdbsum/2lfg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lfg ProSAT]</span></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=2lfg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lfg OCA], [https://pdbe.org/2lfg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lfg RCSB], [https://www.ebi.ac.uk/pdbsum/2lfg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lfg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://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/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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Dagil, R]] | + | [[Category: Dagil R]] |
| - | [[Category: Knudsen, M J]] | + | [[Category: Knudsen MJ]] |
| - | [[Category: Kragelund, B B]] | + | [[Category: Kragelund BB]] |
| - | [[Category: Shea, C O]] | + | [[Category: O'Shea C]] |
| - | [[Category: Teilum, K]] | + | [[Category: Teilum K]] |
| - | [[Category: Cytokine receptor]]
| + | |
| - | [[Category: Extracellular domain]]
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| - | [[Category: Hormone receptor]]
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| Structural highlights
Function
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.[1]
Publication Abstract from PubMed
The prolactin receptor (PRLR) is activated by binding of prolactin in a 2:1 complex, but the activation mechanism is poorly understood. PRLR has a conserved WSXWS motif generic to cytokine class I receptors. We have determined the nuclear magnetic resonance solution structure of the membrane proximal domain of the human PRLR and find that the tryptophans of the motif adopt a T-stack conformation in the unbound state. By contrast, in the hormone bound state, a Trp/Arg-ladder is formed. The conformational change is hormone-dependent and influences the receptor-receptor dimerization site 3. In the constitutively active, breast cancer-related receptor mutant PRLR(I146L), we observed a stabilization of the dimeric state and a change in the dynamics of the motif. Here we demonstrate a structural link between the WSXWS motif, hormone binding, and receptor dimerization and propose it as a general mechanism for class 1 receptor activation.
The WSXWS Motif in Cytokine Receptors Is a Molecular Switch Involved in Receptor Activation: Insight from Structures of the Prolactin Receptor.,Dagil R, Knudsen MJ, Olsen JG, O'Shea C, Franzmann M, Goffin V, Teilum K, Breinholt J, Kragelund BB Structure. 2012 Feb 8;20(2):270-82. PMID:22325776[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Trott JF, Hovey RC, Koduri S, Vonderhaar BK. Alternative splicing to exon 11 of human prolactin receptor gene results in multiple isoforms including a secreted prolactin-binding protein. J Mol Endocrinol. 2003 Feb;30(1):31-47. PMID:12580759
- ↑ Dagil R, Knudsen MJ, Olsen JG, O'Shea C, Franzmann M, Goffin V, Teilum K, Breinholt J, Kragelund BB. The WSXWS Motif in Cytokine Receptors Is a Molecular Switch Involved in Receptor Activation: Insight from Structures of the Prolactin Receptor. Structure. 2012 Feb 8;20(2):270-82. PMID:22325776 doi:http://dx.doi.org/10.1016/j.str.2011.12.010
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