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- EMDB-66514: NPFF bound Mas1 Receptor -

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Basic information

Entry
Database: EMDB / ID: EMD-66514
TitleNPFF bound Mas1 Receptor
Map data
Sample
  • Complex: NPFF bound Mas1 Receptor
    • Protein or peptide: Proto-oncogene Mas
    • Protein or peptide: NPFF
KeywordsGPCR / Agonist / Orphan Receptor / PEPTIDE BINDING PROTEIN
Function / homology
Function and homology information


angiotensin receptor activity / angiotensin type II receptor activity / angiotensin-mediated vasodilation involved in regulation of systemic arterial blood pressure / phospholipase C-activating angiotensin-activated signaling pathway / peptide binding / Peptide ligand-binding receptors / G protein-coupled receptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / regulation of inflammatory response / positive regulation of canonical NF-kappaB signal transduction ...angiotensin receptor activity / angiotensin type II receptor activity / angiotensin-mediated vasodilation involved in regulation of systemic arterial blood pressure / phospholipase C-activating angiotensin-activated signaling pathway / peptide binding / Peptide ligand-binding receptors / G protein-coupled receptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / regulation of inflammatory response / positive regulation of canonical NF-kappaB signal transduction / G protein-coupled receptor signaling pathway / plasma membrane
Similarity search - Function
Proto-oncogene Mas / Mas-related G protein-coupled receptor family / G-protein coupled receptors family 1 signature. / 7 transmembrane receptor (rhodopsin family) / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile.
Similarity search - Domain/homology
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 2.77 Å
AuthorsZhang YM / Liu H / Xu HE
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: EMBO J / Year: 2026
Title: Structural insight into ligand binding and activation of the orphan GPCR Mas1.
Authors: Yumu Zhang / Qiuying Wang / Heng Liu / Hong Shan / Yimin Gu / Jiaqi Yang / Yuan Gao / Kai Wu / Dehua Yang / H Eric Xu /
Abstract: The Mas1 receptor, an orphan class A G-protein-coupled receptor (GPCR), plays pivotal roles in cardiovascular and anti-inflammatory regulation. Despite its therapeutic relevance, the structural ...The Mas1 receptor, an orphan class A G-protein-coupled receptor (GPCR), plays pivotal roles in cardiovascular and anti-inflammatory regulation. Despite its therapeutic relevance, the structural mechanisms underlying Mas1 ligand binding and activation remain poorly understood. Here, we report cryo-EM structures of Mas1 bound to two chemically distinct agonists-neuropeptide FF (NPFF) and synthetic small-molecule AR234958-captured in complex with inhibitory G proteins. These structures reveal a conserved orthosteric binding pocket accommodating both ligands through shared hydrophobic interactions. Unlike many other class A GPCRs that rely on direct W toggle switch engagement, Mas1 adopts a non-canonical activation strategy driven by a ligand-induced hydrophobic compression plane involving residues Y248, L87, I84, and L266 at the bottom of the ligand binding pocket. This mechanism transmits mechanical tension to promote TM6 displacement and G protein coupling. Functional mutagenesis validates this model, identifying two transmembrane helix 6 (TM6) residues, M244 and F237, as critical molecular switches. Comparative analyses of Mas1-related receptors, MRGPRX1-X4, reveal conserved features and mechanistic divergence within this subfamily. These findings provide a structural framework for understanding Mas1 pharmacology and rational design of selective therapeutics.
History
DepositionOct 9, 2025-
Header (metadata) releaseApr 15, 2026-
Map releaseApr 15, 2026-
UpdateApr 15, 2026-
Current statusApr 15, 2026Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_66514.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
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AxesZ (Sec.)Y (Row.)X (Col.)
0.83 Å/pix.
x 256 pix.
= 212.48 Å
0.83 Å/pix.
x 256 pix.
= 212.48 Å
0.83 Å/pix.
x 256 pix.
= 212.48 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.83 Å
Density
Contour LevelBy AUTHOR: 0.7
Minimum - Maximum-9.171811999999999 - 11.153798999999999
Average (Standard dev.)0.0016862234 (±0.14374565)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 212.48 Å
α=β=γ: 90.0 °

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Supplemental data

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Mask #1

Fileemd_66514_msk_1.map
Projections & Slices
AxesZYX

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Half map: #1

Fileemd_66514_half_map_1.map
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Half map: #2

Fileemd_66514_half_map_2.map
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Sample components

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Entire : NPFF bound Mas1 Receptor

EntireName: NPFF bound Mas1 Receptor
Components
  • Complex: NPFF bound Mas1 Receptor
    • Protein or peptide: Proto-oncogene Mas
    • Protein or peptide: NPFF

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Supramolecule #1: NPFF bound Mas1 Receptor

SupramoleculeName: NPFF bound Mas1 Receptor / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Proto-oncogene Mas

MacromoleculeName: Proto-oncogene Mas / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 37.502043 KDa
Recombinant expressionOrganism: Spodoptera frugiperda (fall armyworm)
SequenceString: MDGSNVTSFV VEEPTNISTG RNASVGNAHR QIPIVHWVIM SISPVGFVEN GILLWFLCFR MRRNPFTVYI THLSIADISL LFCIFILSI DYALDYELSS GHYYTIVTLS VTFLFGYNTG LYLLTAISVE RCLSVLYPIW YRCHRPKYQS ALVCALLWAL S CLVTTMEY ...String:
MDGSNVTSFV VEEPTNISTG RNASVGNAHR QIPIVHWVIM SISPVGFVEN GILLWFLCFR MRRNPFTVYI THLSIADISL LFCIFILSI DYALDYELSS GHYYTIVTLS VTFLFGYNTG LYLLTAISVE RCLSVLYPIW YRCHRPKYQS ALVCALLWAL S CLVTTMEY VMCIDREEES HSRNDCRAVI IFIAILSFLV FTPLMLVSST ILVVKIRKNT WASHSSKLYI VIMVTIIIFL IF AMPMRLL YLLYYEYWST FGNLHHISLL FSTINSSANP FIYFFVGSSK KKRFKESLKV VLTRAFKDEM QPRRQKDNCN TVT VETVV

UniProtKB: Proto-oncogene Mas

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Macromolecule #2: NPFF

MacromoleculeName: NPFF / type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 1.08326 KDa
SequenceString:
FLFQPQRF

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration15 mg/mL
BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 1.56 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: DIFFRACTION / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

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Image processing

CTF correctionSoftware - Name: RELION / Type: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 2.77 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 782093
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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