View source for 9jg0


==Cryo-EM structure of neuropeptide FF receptor 2 in the ligand-free state with BRIL fusion, anti-BRIL Fab, and nanobody==
<StructureSection load='9jg0' size='340' side='right'caption='[[9jg0]], [[Resolution|resolution]] 2.91&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9jg0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9JG0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9JG0 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.91&#8491;</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=9jg0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9jg0 OCA], [https://pdbe.org/9jg0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9jg0 RCSB], [https://www.ebi.ac.uk/pdbsum/9jg0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9jg0 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NPFF2_HUMAN NPFF2_HUMAN] Receptor for NPAF (A-18-F-amide) and NPFF (F-8-F-amide) neuropeptides, also known as morphine-modulating peptides. Can also be activated by a variety of naturally occurring or synthetic FMRF-amide like ligands. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.<ref>PMID:11024015</ref> [https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.
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== Publication Abstract from PubMed ==
Neuropeptide FF Receptor 2 (NPFFR2), a G-protein-coupled receptor, plays a role in pain modulation and diet-induced thermogenesis. While NPFFR2 is strongly activated by neuropeptides FF (NPFFs), it shows low activity in response to RF-amide-related peptides (RFRPs), despite the peptides belonging to a shared family. In contrast, NPFFR1, which shares high sequence similarity with NPFFR2, is activated by RFRPs and regulates reproductive hormone balance. The molecular basis for these receptor-specific interactions with their RF-amide peptides remains unclear. Here, we present cryo-electron microscopy structures of NPFFR2 in its active state bound to the agonist RF-amide peptide hNPSF, and in its ligand-free state. Structural analysis reveals that the C-terminal RF-amide moiety engages conserved residues in the transmembrane domain, while the N-terminal segment interacts in a receptor subtype-specific manner. Key selectivity-determining residues in NPFFR2 are also identified. A homology model of NPFFR1 bound to RFRP, supported by mutagenesis studies, further validates this selectivity mechanism. Additionally, structural comparison between the inactive and active states of NPFFR2 suggests a TM3-mediated activation mechanism. These findings provide insights into RF-amide peptide recognition by NPFF receptors.

Structural insights into the selective recognition of RF-amide peptides by neuropeptide FF receptor 2.,Kim J, Hong S, Lee H, Lee HS, Park C, Kim J, Im W, Choi HJ EMBO Rep. 2025 Mar 24. doi: 10.1038/s44319-025-00428-2. PMID:40128413<ref>PMID:40128413</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Choi H-J]]
[[Category: Kim J]]