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- EMDB-26003: Cryo-EM structure of the relaxin receptor RXFP1 in complex with h... -
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Open data
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Basic information
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Title | Cryo-EM structure of the relaxin receptor RXFP1 in complex with heterotrimeric Gs | |||||||||
![]() | Primary map used for model building, generated from a combine focused maps job in Phenix. | |||||||||
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![]() | GPCR / Complex / Signaling / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() lung connective tissue development / nipple morphogenesis / Relaxin receptors / parturition / myofibroblast differentiation / hormone binding / G protein-coupled peptide receptor activity / PKA activation in glucagon signalling / hair follicle placode formation / mu-type opioid receptor binding ...lung connective tissue development / nipple morphogenesis / Relaxin receptors / parturition / myofibroblast differentiation / hormone binding / G protein-coupled peptide receptor activity / PKA activation in glucagon signalling / hair follicle placode formation / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / intracellular transport / D1 dopamine receptor binding / Hedgehog 'off' state / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / hormone-mediated signaling pathway / extracellular matrix organization / trans-Golgi network membrane / G protein-coupled receptor activity / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / bone development / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / platelet aggregation / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / sensory perception of smell / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / positive regulation of cold-induced thermogenesis / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
![]() | Erlandson SC / Rawson S | |||||||||
Funding support | ![]()
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![]() | ![]() Title: The relaxin receptor RXFP1 signals through a mechanism of autoinhibition. Authors: Sarah C Erlandson / Shaun Rawson / James Osei-Owusu / Kelly P Brock / Xinyue Liu / Joao A Paulo / Julian Mintseris / Steven P Gygi / Debora S Marks / Xiaojing Cong / Andrew C Kruse / ![]() ![]() Abstract: The relaxin family peptide receptor 1 (RXFP1) is the receptor for relaxin-2, an important regulator of reproductive and cardiovascular physiology. RXFP1 is a multi-domain G protein-coupled receptor ...The relaxin family peptide receptor 1 (RXFP1) is the receptor for relaxin-2, an important regulator of reproductive and cardiovascular physiology. RXFP1 is a multi-domain G protein-coupled receptor (GPCR) with an ectodomain consisting of a low-density lipoprotein receptor class A (LDLa) module and leucine-rich repeats. The mechanism of RXFP1 signal transduction is clearly distinct from that of other GPCRs, but remains very poorly understood. In the present study, we determine the cryo-electron microscopy structure of active-state human RXFP1, bound to a single-chain version of the endogenous agonist relaxin-2 and the heterotrimeric G protein. Evolutionary coupling analysis and structure-guided functional experiments reveal that RXFP1 signals through a mechanism of autoinhibition. Our results explain how an unusual GPCR family functions, providing a path to rational drug development targeting the relaxin receptors. #1: ![]() Title: The relaxin receptor RXFP1 signals through a mechanism of autoinhibition Authors: Erlandson SC / Rawson S / Osei-Owusu J / Brock KP / Liu X / Paulo JA / Mintseris J / Gygi SP / Marks DS / Cong X / Kruse AC | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 68.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 31.7 KB 31.7 KB | Display Display | ![]() |
Images | ![]() | 43.5 KB | ||
Others | ![]() ![]() ![]() ![]() ![]() ![]() | 80.8 MB 80.2 MB 81 MB 80.8 MB 84.5 MB 84.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 692.7 KB | Display | ![]() |
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Full document | ![]() | 692.2 KB | Display | |
Data in XML | ![]() | 13.3 KB | Display | |
Data in CIF | ![]() | 15.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7tmwMC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Annotation | Primary map used for model building, generated from a combine focused maps job in Phenix. | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.06 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: DeepEMhancer post-processed map generated after 3D focused classifications...
File | emd_26003_additional_1.map | ||||||||||||
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Annotation | DeepEMhancer post-processed map generated after 3D focused classifications of transmembrane helix 1. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: DeepEMhancer post-processed map generated after 3D focused classifications...
File | emd_26003_additional_2.map | ||||||||||||
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Annotation | DeepEMhancer post-processed map generated after 3D focused classifications of extracellular loops. | ||||||||||||
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Density Histograms |
-Additional map: DeepEMhancer post-processed map generated after 3D focused classifications...
File | emd_26003_additional_3.map | ||||||||||||
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Annotation | DeepEMhancer post-processed map generated after 3D focused classifications of extracellular loops. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: DeepEMhancer post-processed map generated after 3D focused classifications...
File | emd_26003_additional_4.map | ||||||||||||
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Annotation | DeepEMhancer post-processed map generated after 3D focused classifications of helix8. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half-map from cryoSPARC refinement for map J8.
File | emd_26003_half_map_1.map | ||||||||||||
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Annotation | Half-map from cryoSPARC refinement for map J8. | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half-map from cryoSPARC refinement for map J8.
File | emd_26003_half_map_2.map | ||||||||||||
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Annotation | Half-map from cryoSPARC refinement for map J8. | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Complex of the relaxin receptor RXFP1 and heterotrimeric Gs
Entire | Name: Complex of the relaxin receptor RXFP1 and heterotrimeric Gs |
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Components |
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-Supramolecule #1: Complex of the relaxin receptor RXFP1 and heterotrimeric Gs
Supramolecule | Name: Complex of the relaxin receptor RXFP1 and heterotrimeric Gs type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Molecular weight | Theoretical: 180 KDa |
-Supramolecule #2: Relaxin receptor 1, Guanine nucleotide-binding protein G(s) subun...
Supramolecule | Name: Relaxin receptor 1, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short fusion type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Supramolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1,...
Supramolecule | Name: 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 type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2-#3 |
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Source (natural) | Organism: ![]() |
-Supramolecule #4: Camelid antibody VHH fragment Nb35
Supramolecule | Name: Camelid antibody VHH fragment Nb35 / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #4 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Relaxin receptor 1, Guanine nucleotide-binding protein G(s) subun...
Macromolecule | Name: Relaxin receptor 1, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short fusion type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 113.442891 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DYKDDDDGGS LEVLFQGPGG SQDVKCSLGY FPCGNITKCL PQLLHCNGVD DCGNQADEDN CGDNNGWSLQ FDKYFASYYK MTSQYPFEA ETPECLVGSV PVQCLCQGLE LDCDETNLRA VPSVSSNVTA MSLQWNLIRK LPPDCFKNYH DLQKLYLQNN K ITSISIYA ...String: DYKDDDDGGS LEVLFQGPGG SQDVKCSLGY FPCGNITKCL PQLLHCNGVD DCGNQADEDN CGDNNGWSLQ FDKYFASYYK MTSQYPFEA ETPECLVGSV PVQCLCQGLE LDCDETNLRA VPSVSSNVTA MSLQWNLIRK LPPDCFKNYH DLQKLYLQNN K ITSISIYA FRGLNSLTKL YLSHNRITFL KPGVFEDLHR LEWLIIEDNH LSRISPPTFY GLNSLILLVL MNNVLTRLPD KP LCQHMPR LHWLDLEGNH IHNLRNLTFI SCSNLTVLVM RKNKINHLNE NTFAPLQKLD ELDLGSNKIE NLPPLIFKDL KEL SQLNLS YNPIQKIQAN QFDYLVKLKS LSLEGIEISN IQQRMFRPLM NLSHIYFKKF QYCGYAPHVR SCKPNTDGIS SLEN LLASI IQRVFVWVVS AVTCFGNIFV ICMRPYIRSE NKLYAMSIIS LCCADCLMGI YLFVIGGFDL KFRGEYNKHA QLWME STHC QLVGSLAILS TEVSVLLLTF LTLEKYICIV YPFRCVRPGK CRTITVLILI WITGFIVAFI PLSNKEFFKN YYGTNG VCF PLHSEDTESI GAQIYSVAIF LGINLAAFII IVFSYGSMFY SVHQSAITAT EIRNQVKKEM ILAKRFFFIV FTDALCW IP IFVVKFLSLL QVEIPGTITS WVVIFILPIN SALNPILYTL TTRPFKEMIH RFWYNYRQRK SMDSKGQKTY APSFIWVE M WPLQEMPPEL MKPDLNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGADN SGKSTIVKQM RIYHGGSGG SGGTSGIFET KFQVDKVNFH MFDVGGQRDE RRKWIQCFND VTAIIFVVDS SDYNRLQEAL NLFKSIWNNR WLRTISVILF LNKQDLLAE KVLAGKSKIE DYFPEFARYT TPEDATPEPG EDPRVTRAKY FIRDEFLRIS TASGDGRHYC YPHFTCAVDT E NARRIFND CRDIIQRMHL RQYELL UniProtKB: Relaxin receptor 1, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short |
-Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 38.534062 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV ...String: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV TSSGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD IN AICFFPN GNAFATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAG HDNRVS CLGVTDDGMA VATGSWDSFL KIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #4: Camelid antibody VHH fragment Nb35
Macromolecule | Name: Camelid antibody VHH fragment Nb35 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 17.444324 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSSL EVLFQGPGHH HHHHHHGSED QVDPRLIDGK |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.2 mg/mL |
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Buffer | pH: 7.5 |
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 400 / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 283.15 K / Instrument: FEI VITROBOT MARK IV |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 52.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.3000000000000003 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 81000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |