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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-30665 | |||||||||
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Title | Cryo-EM structure of histamine H1 receptor Gq complex | |||||||||
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Function / homology | ![]() Histamine receptors / histamine receptor activity / cellular response to histamine / regulation of vascular permeability / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / positive regulation of vasoconstriction / visual learning / Olfactory Signaling Pathway ...Histamine receptors / histamine receptor activity / cellular response to histamine / regulation of vascular permeability / G protein-coupled serotonin receptor activity / neurotransmitter receptor activity / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / positive regulation of vasoconstriction / visual learning / Olfactory Signaling Pathway / Activation of the phototransduction cascade / regulation of synaptic plasticity / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / 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 / memory / 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 / 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 / chemical synaptic transmission / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / inflammatory response / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / dendrite / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | |||||||||
![]() | He Y / Xia R / Wang N / Xu Z | |||||||||
![]() | ![]() Title: Cryo-EM structure of the human histamine H receptor/G complex. Authors: Ruixue Xia / Na Wang / Zhenmei Xu / Yang Lu / Jing Song / Anqi Zhang / Changyou Guo / Yuanzheng He / ![]() Abstract: Histamine receptors play important roles in various pathophysiological conditions and are effective targets for anti-allergy treatment, however the mechanism of receptor activation remain elusive. ...Histamine receptors play important roles in various pathophysiological conditions and are effective targets for anti-allergy treatment, however the mechanism of receptor activation remain elusive. Here, we present the cryo-electron microscopy (cryo-EM) structure of the human HR in complex with a G protein in an active conformation via a NanoBiT tethering strategy. The structure reveals that histamine activates receptor via interacting with the key residues of both transmembrane domain 3 (TM3) and TM6 to squash the binding pocket on the extracellular side and to open the cavity on the intracellular side for G engagement in a model of "squash to activate and expand to deactivate". The structure also reveals features for G coupling, including the interaction between intracellular loop 2 (ICL2) and the αN-β junction of G protein. The detailed analysis of our structure will provide a framework for understanding G-protein coupling selectivity and clues for designing novel antihistamines. | |||||||||
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 | ![]() | 33 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.5 KB 14.5 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.1 KB | Display | ![]() |
Images | ![]() | 69 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7dflMC 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: 1.08 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 : GPCR/G-protein complex
Entire | Name: GPCR/G-protein complex |
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Components |
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-Supramolecule #1: GPCR/G-protein complex
Supramolecule | Name: GPCR/G-protein complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: ![]() |
Recombinant expression | Organism: ![]() ![]() |
Molecular weight | Theoretical: 130 kDa/nm |
-Macromolecule #1: Histamine H1 receptor
Macromolecule | Name: Histamine H1 receptor / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 55.856035 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MSLPNSSCLL EDKMCEGNKT TMASPQLMPL VVVLSTICLV TVGLNLLVLY AVRSERKLHT VGNLYIVSLS VADLIVGAVV MPMNILYLL MSKWSLGRPL CLFWLSMDYV ASTASIFSVF ILCIDRYRSV QQPLRYLKYR TKTRASATIL GAWFLSFLWV I PILGWNHF ...String: MSLPNSSCLL EDKMCEGNKT TMASPQLMPL VVVLSTICLV TVGLNLLVLY AVRSERKLHT VGNLYIVSLS VADLIVGAVV MPMNILYLL MSKWSLGRPL CLFWLSMDYV ASTASIFSVF ILCIDRYRSV QQPLRYLKYR TKTRASATIL GAWFLSFLWV I PILGWNHF MQQTSVRRED KCETDFYDVT WFKVMTAIIN FYLPTLLMLW FYAKIYKAVR QHCQHRELIN RSLPSFSEIK LR PENPKGD AKKPGKESPW EVLKRKPKDA GGGSVLKSPS QTPKEMKSPV VFSQEDDREV DKLYCFPLDI VHMQAAAEGS SRD YVAVNR SHGQLKTDEQ GLNTHGASEI SEDQMLGDSQ SFSRTDSDTT TETAPGKGKL RSGSNTGLDY IKFTWKRLRS HSRQ YVSGL HMNRERKAAK QLGFIMAAFI LCWIPYFIFF MVIAFCKNCC NEHLHMFTIW LGYINSTLNP LIYPLCNENF KKTFK RILH IRS |
-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: 37.285734 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLII WDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR FLDDNQIVTS S GDTTCALW ...String: SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLII WDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR FLDDNQIVTS S GDTTCALW DIETGQQTTT FTGHTGDVMS LSLAPDTRLF VSGACDASAK LWDVREGMCR QTFTGHESDI NAICFFPNGN AF ATGSDDA TCRLFDLRAD QELMTYSHDN IICGITSVSF SKSGRLLLAG YDDFNCNVWD ALKADRAGVL AGHDNRVSCL GVT DDGMAV ATGSWDSFLK IWN |
-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: 6.375332 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: NTASIAQARK LVEQLKMEAN IDRIKVSKAA ADLMAYCEAH AKEDPLLTPV PASENPFR |
-Macromolecule #4: Guanine nucleotide-binding protein G(q) subunit alpha
Macromolecule | Name: Guanine nucleotide-binding protein G(q) subunit alpha / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 41.090637 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: CTLSAEDKAA VERSKMIDRN LREDGEKARR ELKLLLLGTG ESGKSTFIKQ MRIIHGSGYS DEDKRGFTKL VYQNIFTAMQ AMIRAMDTL KIPYKHEHNK AHAQLVREVD VEKVSTFENP YVDAIRSLWS DPGIQECYDR RREYQLSDST KYYLNDLDRI A DSTYLPTQ ...String: CTLSAEDKAA VERSKMIDRN LREDGEKARR ELKLLLLGTG ESGKSTFIKQ MRIIHGSGYS DEDKRGFTKL VYQNIFTAMQ AMIRAMDTL KIPYKHEHNK AHAQLVREVD VEKVSTFENP YVDAIRSLWS DPGIQECYDR RREYQLSDST KYYLNDLDRI A DSTYLPTQ QDVLRVRVPT TGIIEYPFDL QSVIFRMVDV GGQRSERRKW IHCFENVTSI MFLVALSEYD QVLVESDNEN RM EESKALF RTIITYPWFQ NSSVILFLNK KDLLEEKIMY SHLVDYFPEY DGPQRDAQAA REFILKMFVD LNPDSDKILY SHF TCATDT ENIRFVFAAV KDTILQLNLK EYNLV |
-Macromolecule #5: scFv16
Macromolecule | Name: scFv16 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 26.679721 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...String: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KAAA |
-Macromolecule #6: HISTAMINE
Macromolecule | Name: HISTAMINE / type: ligand / ID: 6 / Number of copies: 1 / Formula: HSM |
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Molecular weight | Theoretical: 111.145 Da |
Chemical component information | ![]() ChemComp-HSM: |
-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 / Chamber humidity: 100 % |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 56.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 0.01 mm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |