2lfg: Difference between revisions
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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 | <StructureSection load='2lfg' size='340' side='right'caption='[[2lfg]]' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
[[2lfg]] is a 1 chain structure with sequence from [ | <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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | ||
<b> | <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> | |||
== 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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | == 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 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. | ||
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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<ref>PMID:22325776</ref> | 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<ref>PMID:22325776</ref> | ||
From | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
<div class="pdbe-citations 2lfg" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Prolactin receptor|Prolactin receptor]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Dagil | [[Category: Large Structures]] | ||
[[Category: Knudsen | [[Category: Dagil R]] | ||
[[Category: Kragelund | [[Category: Knudsen MJ]] | ||
[[Category: Shea | [[Category: Kragelund BB]] | ||
[[Category: Teilum | [[Category: O'Shea C]] | ||
[[Category: Teilum K]] | |||
