2lfg: Difference between revisions

Latest revision as of 05:42, 15 May 2024

Solution structure of the human prolactin receptor ecd domain d2

Structural highlights

2lfg is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

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:https://dx.doi.org/10.1016/j.str.2011.12.010

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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:https://dx.doi.org/10.1016/j.str.2011.12.010

[1]

[2]

@@ Line 1: / Line 1: @@
-[[Image:2lfg.png|left|200px]]
-<!--
+==Solution structure of the human prolactin receptor ecd domain d2==
-The line below this paragraph, containing "STRUCTURE_2lfg", creates the "Structure Box" on the page.
+<StructureSection load='2lfg' size='340' side='right'caption='[[2lfg]]' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<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>
-or leave the SCENE parameter empty for the default display.
+</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='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>
-{{STRUCTURE_2lfg|  PDB=2lfg  |  SCENE=  }}
+</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 ==
+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.
-===Solution structure of the human prolactin receptor ecd domain d2===
+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 MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2lfg" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_22325776}}, adds the Publication Abstract to the page
+*[[Prolactin receptor|Prolactin receptor]]
-(as it appears on PubMed at http://www.pubmed.gov), where 22325776 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_22325776}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[2lfg]] is a 1 chain structure with sequence from [http://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].
-==Reference==
-<ref group="xtra">PMID:022325776</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Dagil, R.]]
+[[Category: Large Structures]]
-[[Category: Knudsen, M J.]]
+[[Category: Dagil R]]
-[[Category: Kragelund, B B.]]
+[[Category: Knudsen MJ]]
-[[Category: Shea, C O.]]
+[[Category: Kragelund BB]]
-[[Category: Teilum, K.]]
+[[Category: O'Shea C]]
-[[Category: Cytokine receptor]]
+[[Category: Teilum K]]
-[[Category: Extracellular domain]]
-[[Category: Hormone receptor]]

2lfg: Difference between revisions

Latest revision as of 05:42, 15 May 2024

Solution structure of the human prolactin receptor ecd domain d2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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