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| | ==Crystal structure of a prolactin receptor antagonist bound to the extracellular domain of the prolactin receptor== | | ==Crystal structure of a prolactin receptor antagonist bound to the extracellular domain of the prolactin receptor== |
| - | <StructureSection load='3d48' size='340' side='right' caption='[[3d48]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='3d48' size='340' side='right'caption='[[3d48]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3d48]] 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=3D48 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3D48 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3d48]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3D48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3D48 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO3:CARBONATE+ION'>CO3</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1bp3|1bp3]], [[1f6f|1f6f]], [[1rw5|1rw5]], [[1n9d|1n9d]], [[2q98|2q98]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1bp3|1bp3]], [[1f6f|1f6f]], [[1rw5|1rw5]], [[1n9d|1n9d]], [[2q98|2q98]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PRLR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PRL ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PRLR ([https://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3d48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d48 OCA], [http://pdbe.org/3d48 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3d48 RCSB], [http://www.ebi.ac.uk/pdbsum/3d48 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3d48 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=3d48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3d48 OCA], [https://pdbe.org/3d48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3d48 RCSB], [https://www.ebi.ac.uk/pdbsum/3d48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3d48 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. [[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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Breinholt, J]] | | [[Category: Breinholt, J]] |
| | [[Category: Svensson, L A]] | | [[Category: Svensson, L A]] |
| Structural highlights
Function
[PRL_HUMAN] Prolactin acts primarily on the mammary gland by promoting lactation. [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]
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
The crystal structure of the complex between an N-terminally truncated G129R human prolactin (PRL) variant and the extracellular domain of the human prolactin receptor (PRLR) was determined at 2.5A resolution by x-ray crystallography. This structure represents the first experimental structure reported for a PRL variant bound to its cognate receptor. The binding of PRL variants to the PRLR extracellular domain was furthermore characterized by the solution state techniques, hydrogen exchange mass spectrometry, and NMR spectroscopy. Compared with the binding interface derived from mutagenesis studies, the structural data imply that the definition of PRL binding site 1 should be extended to include residues situated in the N-terminal part of loop 1 and in the C terminus. Comparison of the structure of the receptor-bound PRL variant with the structure reported for the unbound form of a similar analogue ( Jomain, J. B., Tallet, E., Broutin, I., Hoos, S., van Agthoven, J., Ducruix, A., Kelly, P. A., Kragelund, B. B., England, P., and Goffin, V. (2007) J. Biol. Chem. 282, 33118-33131 ) demonstrates that receptor-induced changes in the backbone of the four-helix bundle are subtle, whereas large scale rearrangements and structuring occur in the flexible N-terminal part of loop 1. Hydrogen exchange mass spectrometry data imply that the dynamics of the four-helix bundle in solution generally become stabilized upon receptor interaction at binding site 1.
Crystal structure of a prolactin receptor antagonist bound to the extracellular domain of the prolactin receptor.,Svensson LA, Bondensgaard K, Norskov-Lauritsen L, Christensen L, Becker P, Andersen MD, Maltesen MJ, Rand KD, Breinholt J J Biol Chem. 2008 Jul 4;283(27):19085-94. Epub 2008 May 8. PMID:18467331[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
- ↑ Svensson LA, Bondensgaard K, Norskov-Lauritsen L, Christensen L, Becker P, Andersen MD, Maltesen MJ, Rand KD, Breinholt J. Crystal structure of a prolactin receptor antagonist bound to the extracellular domain of the prolactin receptor. J Biol Chem. 2008 Jul 4;283(27):19085-94. Epub 2008 May 8. PMID:18467331 doi:10.1074/jbc.M801202200
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