9M2F

Structure of neuropeptide FF receptor 1 complex with NPFF

9M2F の概要

• エントリーDOI: 10.2210/pdb9m2f/pdb
• EMDBエントリー: 63584
• 分子名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, neuropeptide FF, ... (6 entities in total)
• 機能のキーワード: gpcr, npffr1, npvf, npff, membrane protein/immune system, membrane protein-immune system complex
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 174700.47

構造登録者

Pan, B.X.,Jiang, Y.,Li, X.Z. (登録日: 2025-02-27, 公開日: 2025-07-23, 最終更新日: 2025-09-03)

主引用文献

Li, X.,Zhang, H.,Hu, W.,Wu, K.,Li, S.,Jin, S.,Yin, Y.,Yuan, Q.,Xu, H.E.,Pan, B.,Jiang, Y.
Structural basis of peptide recognition and modulation for neuropeptide FF receptors.
Cell Rep, 44:116160-116160, 2025

PubMed Abstract: Neuropeptide FF receptors 1 and 2 (NPFFR1 and NPFFR2) are RF-amide peptide receptors that couple to G proteins and regulate pain, opioid tolerance, and metabolism. Despite their physiological significance, their ligand selectivity and activation mechanisms remain unclear. Using cryoelectron microscopy, we resolved four NPFFR1 and NPFFR2 structures bound to NPFF or NPVF, revealing conserved C-terminal RF-amide interactions within the orthosteric pocket and N-terminal variations driving subtype specificity. Structural and mutagenesis analyses identified ECL2 and the receptor N terminus as key determinants of NPVF-NPFFR1 and NPFF-NPFFR2 selectivity. Additionally, the structures elucidate the activation mechanism and uncover distinct G-coupling features between NPFFR subtypes. These findings provide molecular insights into peptide recognition and receptor activation within the RF-amide family, offering a structural framework for designing selective NPFFR modulators to treat pain, addiction, and metabolic disorders with enhanced specificity and reduced off-target effects.

PubMed: 40839429
DOI: 10.1016/j.celrep.2025.116160

実験手法

ELECTRON MICROSCOPY (2.93 Å)