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| | ==The solution NMR structure of the relaxin (RXFP1) receptor LDLa module.== | | ==The solution NMR structure of the relaxin (RXFP1) receptor LDLa module.== |
| - | <StructureSection load='2jm4' size='340' side='right'caption='[[2jm4]], [[NMR_Ensembles_of_Models | 24 NMR models]]' scene=''> | + | <StructureSection load='2jm4' size='340' side='right'caption='[[2jm4]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2jm4]] 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=2JM4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JM4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2jm4]] 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=2JM4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JM4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></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">RXFP1, LGR7 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></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=2jm4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jm4 OCA], [https://pdbe.org/2jm4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jm4 RCSB], [https://www.ebi.ac.uk/pdbsum/2jm4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jm4 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=2jm4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jm4 OCA], [https://pdbe.org/2jm4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jm4 RCSB], [https://www.ebi.ac.uk/pdbsum/2jm4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jm4 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/RXFP1_HUMAN RXFP1_HUMAN]] Receptor for relaxins. The activity of this receptor is mediated by G proteins leading to stimulation of adenylate cyclase and an increase of cAMP. Binding of the ligand may also activate a tyrosine kinase pathway that inhibits the activity of a phosphodiesterase that degrades cAMP.
| + | [https://www.uniprot.org/uniprot/RXFP1_HUMAN RXFP1_HUMAN] Receptor for relaxins. The activity of this receptor is mediated by G proteins leading to stimulation of adenylate cyclase and an increase of cAMP. Binding of the ligand may also activate a tyrosine kinase pathway that inhibits the activity of a phosphodiesterase that degrades cAMP. |
| | == 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: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Bathgate, R A.D]] | + | [[Category: Bathgate RAD]] |
| - | [[Category: Gooley, P R]] | + | [[Category: Gooley PR]] |
| - | [[Category: Hopkins, E J]] | + | [[Category: Hopkins EJ]] |
| - | [[Category: Ldl-a module]]
| + | |
| - | [[Category: Lgr7]]
| + | |
| - | [[Category: Rxfp1 receptor]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
RXFP1_HUMAN Receptor for relaxins. The activity of this receptor is mediated by G proteins leading to stimulation of adenylate cyclase and an increase of cAMP. Binding of the ligand may also activate a tyrosine kinase pathway that inhibits the activity of a phosphodiesterase that degrades cAMP.
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 receptors for the peptide hormones relaxin and insulin-like peptide 3 (INSL3) are the leucine-rich repeat-containing G-protein-coupled receptors LGR7 and LGR8 recently renamed as the relaxin family peptide (RXFP) receptors, RXFP1 and RXFP2, respectively. These receptors differ from other LGRs by the addition of an N-terminal low density lipoprotein receptor class A (LDLa) module and are the only human G-protein-coupled receptors to contain such a domain. Recently it was shown that the LDLa module of the RXFP1 and RXFP2 receptors is essential for ligand-stimulated cAMP signaling. The mechanism by which the LDLa module modulates receptor signaling is unknown; however, it represents a unique paradigm in understanding G-protein-coupled receptor signaling. Here we present the structure of the RXFP1 receptor LDLa module determined by solution NMR spectroscopy. The structure is similar to other LDLa modules but shows small differences in side chain orientations and inter-residue packing. Interchange of the module with the second ligand binding domain of the LDL receptor, LB2, results in a receptor that binds relaxin with full affinity but is unable to signal. Furthermore, we demonstrate via structural studies on mutated LDLa modules and functional studies on mutated full-length receptors that a hydrophobic surface within the N-terminal region of the module is essential for activation of RXFP1 receptor signal in response to relaxin stimulation. This study has highlighted the necessity to understand the structural effects of single amino acid mutations on the LDLa module to fully interpret the effects of these mutations on receptor activity.
The NMR solution structure of the relaxin (RXFP1) receptor lipoprotein receptor class A module and identification of key residues in the N-terminal region of the module that mediate receptor activation.,Hopkins EJ, Layfield S, Ferraro T, Bathgate RA, Gooley PR J Biol Chem. 2007 Feb 9;282(6):4172-84. Epub 2006 Dec 4. PMID:17148455[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hopkins EJ, Layfield S, Ferraro T, Bathgate RA, Gooley PR. The NMR solution structure of the relaxin (RXFP1) receptor lipoprotein receptor class A module and identification of key residues in the N-terminal region of the module that mediate receptor activation. J Biol Chem. 2007 Feb 9;282(6):4172-84. Epub 2006 Dec 4. PMID:17148455 doi:10.1074/jbc.M609526200
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