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- EMDB-31480: Cryo-EM structure of human bradykinin receptor BK2R in complex Gq... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-31480 | |||||||||||||||||||||
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Title | Cryo-EM structure of human bradykinin receptor BK2R in complex Gq proteins and bradykinin | |||||||||||||||||||||
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Function / homology | ![]() Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / PLC beta mediated events / phospholipase C-activating dopamine receptor signaling pathway / entrainment of circadian clock / regulation of platelet activation / phototransduction, visible light / glutamate receptor signaling pathway / regulation of canonical Wnt signaling pathway / action potential ...Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / PLC beta mediated events / phospholipase C-activating dopamine receptor signaling pathway / entrainment of circadian clock / regulation of platelet activation / phototransduction, visible light / glutamate receptor signaling pathway / regulation of canonical Wnt signaling pathway / action potential / : / photoreceptor outer segment / GTPase activator activity / G protein-coupled receptor binding / negative regulation of protein kinase activity / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / 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 / 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 / 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 / blood coagulation / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / nuclear membrane / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / protein stabilization / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / GTP binding / Golgi apparatus / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||||||||||||||
Biological species | ![]() | |||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.9 Å | |||||||||||||||||||||
![]() | Shen J / Zhang D / Fu Y / Chen A / Zhang H | |||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM structures of human bradykinin receptor-G proteins complexes. Authors: Jinkang Shen / Dongqi Zhang / Yao Fu / Anqi Chen / Xiaoli Yang / Haitao Zhang / ![]() Abstract: The type 2 bradykinin receptor (B2R) is a G protein-coupled receptor (GPCR) in the cardiovascular system, and the dysfunction of B2R leads to inflammation, hereditary angioedema, and pain. Bradykinin ...The type 2 bradykinin receptor (B2R) is a G protein-coupled receptor (GPCR) in the cardiovascular system, and the dysfunction of B2R leads to inflammation, hereditary angioedema, and pain. Bradykinin and kallidin are both endogenous peptide agonists of B2R, acting as vasodilators to protect the cardiovascular system. Here we determine two cryo-electron microscopy (cryo-EM) structures of human B2R-G in complex with bradykinin and kallidin at 3.0 Å and 2.9 Å resolution, respectively. The ligand-binding pocket accommodates S-shaped peptides, with aspartic acids and glutamates as an anion trap. The phenylalanines at the tail of the peptides induce significant conformational changes in the toggle switch W283, the conserved PIF, DRY, and NPxxY motifs, for the B2R activation. This further induces the extensive interactions of the intracellular loops ICL2/3 and helix 8 with G proteins. Our structures elucidate the molecular mechanisms for the ligand binding, receptor activation, and G proteins coupling of B2R. | |||||||||||||||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 4.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15.7 KB 15.7 KB | Display Display | ![]() |
Images | ![]() | 128.5 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7f6hMC ![]() 7f6iC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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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Voxel size | X=Y=Z: 1.014 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : Bradykinin receptor BK2RR in complex with Gq proteins and bradykinin
Entire | Name: Bradykinin receptor BK2RR in complex with Gq proteins and bradykinin |
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Components |
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-Supramolecule #1: Bradykinin receptor BK2RR in complex with Gq proteins and bradykinin
Supramolecule | Name: Bradykinin receptor BK2RR in complex with Gq proteins and bradykinin type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 173 KDa |
-Macromolecule #1: Bradykinin receptor BK2R
Macromolecule | Name: Bradykinin receptor BK2R / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 86.464734 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MKTIIALSYI FCLVFADYKD DDDKHHHHHH HHHHENLYFQ GKIEEGKLVI WINGDKGYNG LAEVGKKFEK DTGIKVTVEH PDKLEEKFP QVAATGDGPD IIFWAHDRFG GYAQSGLLAE ITPDKAFQDK LYPFTWDAVR YNGKLIAYPI AVEALSLIYN K DLLPNPPK ...String: MKTIIALSYI FCLVFADYKD DDDKHHHHHH HHHHENLYFQ GKIEEGKLVI WINGDKGYNG LAEVGKKFEK DTGIKVTVEH PDKLEEKFP QVAATGDGPD IIFWAHDRFG GYAQSGLLAE ITPDKAFQDK LYPFTWDAVR YNGKLIAYPI AVEALSLIYN K DLLPNPPK TWEEIPALDK ELKAKGKSAL MFNLQEPYFT WPLIAADGGY AFKYAAGKYD IKDVGVDNAG AKAGLTFLVD LI KNKHMNA DTDYSIAEAA FNKGETAMTI NGPWAWSNID TSAVNYGVTV LPTFKGQPSK PFVGVLSAGI NAASPNKELA KEF LENYLL TDEGLEAVNK DKPLGAVALK SYEEELAKDP RIAATMENAQ KGEIMPNIPQ MSAFWYAVRT AVINAASGRQ TVDE ALKDA QTLNVTLQGP TLNGTFAQSK CPQVEWLGWL NTIQPPFLWV LFVLATLENI FVLSVFCLHK SSCTVAEIYL GNLAA ADLI LACGLPFWAI TISNNFDWLF GETLCRVVNA IISMNLYSSI CFLMLVSIDR YLALVKTMSM GRMRGVRWAK LYSLVI WGC TLLLSSPMLV FRTMKEYSDE GHNVTACVIS YPSLIWEVFT NMLLNVVGFL LPLSVITFCT MQIMQVLRNN EMQKFKE IQ TERRATVLVL VVLLLFIICW LPFQISTFLD TLHRLGILSS CQDERIIDVI TQIASFMAYS NSCLNPLVYV IVGKRFRK K SWEVYQGVCQ KGGCRSEPIQ MENSMGTLRT SISVERQIHK LQDWAGSRQ |
-Macromolecule #2: Bradykinin
Macromolecule | Name: Bradykinin / type: protein_or_peptide / ID: 2 Details: This peptide is the ligand of the protein bradykinin receptor B2R Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 1.062224 KDa |
Sequence | String: RPPGFSPFR |
-Macromolecule #3: Guanine nucleotide-binding protein G(q) subunit alpha
Macromolecule | Name: Guanine nucleotide-binding protein G(q) subunit alpha / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 43.534449 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MHHHHHHHHH HTLESIMACC LSEEAKEARR INDEIERQLR RDKRDARREL KLLLLGTGES GKSTFIKQMR IIHGSGYSDE DKRGFTKLV YQNIFTAMQA MIRAMDTLKI PYKYEHNKAH AQLVREVDVE KVSAFENPYV DAIKSLWNDP GIQECYDRRR E YQLSDSTK ...String: MHHHHHHHHH HTLESIMACC LSEEAKEARR INDEIERQLR RDKRDARREL KLLLLGTGES GKSTFIKQMR IIHGSGYSDE DKRGFTKLV YQNIFTAMQA MIRAMDTLKI PYKYEHNKAH AQLVREVDVE KVSAFENPYV DAIKSLWNDP GIQECYDRRR E YQLSDSTK YYLNDLDRVA DPAYLPTQQD VLRVQVPTTG IIEYPFDLQS VIFRMVDVGG LRSERRKWIH CFENVTSIMF LV ALSEYDQ VLVESDNENR MEESKALFRT IITYPWFQNS SVILFLNKKD LLEEKIMYSH LVDYFPEYDG PQRDAQAARE FIL KMFVDL NPDSDKIIYS HFTCATDTEN IRFVFAAVKD TILQLNLKEY NLV |
-Macromolecule #4: 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: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 39.086641 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MHHHHHHHHH HGSSGSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHLA KIYAMHWGTD SRLLVSASQ DGKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN LKTREGNVRV SRELAGHTGY L SCCRFLDD ...String: MHHHHHHHHH HGSSGSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHLA KIYAMHWGTD SRLLVSASQ DGKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN LKTREGNVRV SRELAGHTGY L SCCRFLDD NQIVTSSGDT TCALWDIETG QQTTTFTGHT GDVMSLSLAP DTRLFVSGAC DASAKLWDVR EGMCRQTFTG HE SDINAIC FFPNGNAFAT GSDDATCRLF DLRADQELMT YSHDNIICGI TSVSFSKSGR LLLAGYDDFN CNVWDALKAD RAG VLAGHD NRVSCLGVTD DGMAVATGSW DSFLKIWN |
-Macromolecule #5: 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: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 9.242612 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MHHHHHHHHH HASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-Macromolecule #6: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 6 / Number of copies: 2 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 BASE (4k x 4k) / Average electron dose: 64.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.9 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 3960198 |
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Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |