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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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Function / homology | ![]() lung connective tissue development / nipple morphogenesis / Relaxin receptors / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | 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 |
-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. | ||||||||||||
Projections & Slices |
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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 | ![]() |
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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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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 52.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Particle selection | Number selected: 15826542 |
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Startup model | Type of model: OTHER / Details: Ab initio model generated in RELION |
Initial angle assignment | Type: RANDOM ASSIGNMENT / Software - Name: RELION (ver. 3.1) |
Final angle assignment | Type: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. v3.1.0) |
Final reconstruction | Applied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.2 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. v3.1.0) / Number images used: 188250 |