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Yorodumi- EMDB-37823: Cryo-EM structure of Melanin-Concentrating Hormone Receptor 1 with MCH -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-37823 | |||||||||
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Title | Cryo-EM structure of Melanin-Concentrating Hormone Receptor 1 with MCH | |||||||||
Map data | ||||||||||
Sample |
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Keywords | Melanin-Concentrating Hormone Receptors1 / GPCR / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information melanin-concentrating hormone receptor activity / melanin-concentrating hormone activity / type 1 melanin-concentrating hormone receptor binding / neuropeptide receptor activity / hormone binding / BBSome-mediated cargo-targeting to cilium / neuropeptide binding / positive regulation of calcium ion transport / non-motile cilium / feeding behavior ...melanin-concentrating hormone receptor activity / melanin-concentrating hormone activity / type 1 melanin-concentrating hormone receptor binding / neuropeptide receptor activity / hormone binding / BBSome-mediated cargo-targeting to cilium / neuropeptide binding / positive regulation of calcium ion transport / non-motile cilium / feeding behavior / ciliary membrane / Adenylate cyclase inhibitory pathway / neuropeptide signaling pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / generation of precursor metabolites and energy / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / 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 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / response to peptide hormone / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / cilium / 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 / GDP binding / 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 / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / cell cortex / midbody / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / spermatogenesis / G alpha (q) signalling events / chemical synaptic transmission / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell differentiation / cell surface receptor signaling pathway / neuron projection / cell cycle / G protein-coupled receptor signaling pathway / cell division / lysosomal membrane / signaling receptor binding / GTPase activity / centrosome / synapse / protein-containing complex binding / nucleolus / GTP binding / magnesium ion binding / signal transduction Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.01 Å | |||||||||
Authors | Zhao L / He Q / Yuan Q / Gu Y / Shan H / Hu W / Wu K / Xu HE / Zhang Y / Wu C / Shen J | |||||||||
Funding support | China, 1 items
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Citation | Journal: Cell Discov / Year: 2024 Title: Mechanisms of ligand recognition and activation of melanin-concentrating hormone receptors. Authors: Qian He / Qingning Yuan / Hong Shan / Canrong Wu / Yimin Gu / Kai Wu / Wen Hu / Yumu Zhang / Xinheng He / H Eric Xu / Li-Hua Zhao / Abstract: Melanin-concentrating hormone (MCH) is a cyclic neuropeptide that regulates food intake, energy balance, and other physiological functions by stimulating MCHR1 and MCHR2 receptors, both of which are ...Melanin-concentrating hormone (MCH) is a cyclic neuropeptide that regulates food intake, energy balance, and other physiological functions by stimulating MCHR1 and MCHR2 receptors, both of which are class A G protein-coupled receptors. MCHR1 predominately couples to inhibitory G protein, G, and MCHR2 can only couple to G. Here we present cryo-electron microscopy structures of MCH-activated MCHR1 with G and MCH-activated MCHR2 with G at the global resolutions of 3.01 Å and 2.40 Å, respectively. These structures reveal that MCH adopts a consistent cysteine-mediated hairpin loop configuration when bound to both receptors. A central arginine from the LGRVY core motif between the two cysteines of MCH penetrates deeply into the transmembrane pocket, triggering receptor activation. Integrated with mutational and functional insights, our findings elucidate the molecular underpinnings of ligand recognition and MCH receptor activation and offer a structural foundation for targeted drug design. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_37823.map.gz | 6.6 MB | EMDB map data format | |
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Header (meta data) | emd-37823-v30.xml emd-37823.xml | 20.1 KB 20.1 KB | Display Display | EMDB header |
Images | emd_37823.png | 82.8 KB | ||
Filedesc metadata | emd-37823.cif.gz | 6.5 KB | ||
Others | emd_37823_half_map_1.map.gz emd_37823_half_map_2.map.gz | 49.6 MB 49.6 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-37823 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-37823 | HTTPS FTP |
-Validation report
Summary document | emd_37823_validation.pdf.gz | 819.3 KB | Display | EMDB validaton report |
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Full document | emd_37823_full_validation.pdf.gz | 818.9 KB | Display | |
Data in XML | emd_37823_validation.xml.gz | 12.2 KB | Display | |
Data in CIF | emd_37823_validation.cif.gz | 14.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37823 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-37823 | HTTPS FTP |
-Related structure data
Related structure data | 8wssMC 8wstC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_37823.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 0.824 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_37823_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_37823_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Mechanisms of Ligand Recognition and Activation of Melanin-Concen...
Entire | Name: Mechanisms of Ligand Recognition and Activation of Melanin-Concentrating Hormone Receptors1 |
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Components |
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-Supramolecule #1: Mechanisms of Ligand Recognition and Activation of Melanin-Concen...
Supramolecule | Name: Mechanisms of Ligand Recognition and Activation of Melanin-Concentrating Hormone Receptors1 type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 160 KDa |
-Macromolecule #1: Guanine nucleotide-binding protein G(i) subunit alpha-1
Macromolecule | Name: Guanine nucleotide-binding protein G(i) subunit alpha-1 type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 40.414047 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKNTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHASM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-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: Homo sapiens (human) |
Molecular weight | Theoretical: 41.055867 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI ...String: MHHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI VTSSGDTTCA LWDIETGQQT TTFTGHTGDV MSLSLAPDTR LFVSGACDAS AKLWDVREGM CRQTFTGHES DI NAICFFP NGNAFATGSD DATCRLFDLR ADQELMTYSH DNIICGITSV SFSKSGRLLL AGYDDFNCNV WDALKADRAG VLA GHDNRV SCLGVTDDGM AVATGSWDSF LKIWNGSSGG GGSGGGGSSG VSGWRLFKKI S 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: Homo sapiens (human) |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
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: Scfv16
Macromolecule | Name: Scfv16 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Mus musculus (house mouse) |
Molecular weight | Theoretical: 30.363043 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFAVQ LVESGGGLVQ PGGSRKLSCS ASGFAFSSFG MHWVRQAPEK GLEWVAYIS SGSGTIYYAD TVKGRFTISR DDPKNTLFLQ MTSLRSEDTA MYYCVRSIYY YGSSPFDFWG QGTTLTVSAG G GGSGGGGS ...String: MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFAVQ LVESGGGLVQ PGGSRKLSCS ASGFAFSSFG MHWVRQAPEK GLEWVAYIS SGSGTIYYAD TVKGRFTISR DDPKNTLFLQ MTSLRSEDTA MYYCVRSIYY YGSSPFDFWG QGTTLTVSAG G GGSGGGGS GGGGSADIVM TQATSSVPVT PGESVSISCR SSKSLLHSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DR FSGSGSG TAFTLTISRL EAEDVGVYYC MQHLEYPLTF GAGTKLEL |
-Macromolecule #5: Pro-MCH
Macromolecule | Name: Pro-MCH / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 2.391879 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: DFDMLRCMLG RVYRPCWQV UniProtKB: Pro-MCH |
-Macromolecule #6: Melanin-concentrating hormone receptor 1
Macromolecule | Name: Melanin-concentrating hormone receptor 1 / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 43.716758 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: QGGTMDLEAS LLPTGPNASN TSDGPDNLTS AGSPPRTGSI SYINIIMPSV FGTICLLGII GNSTVIFAVV KKSKLHWCNN VPDIFIINL SVVDLLFLLG MPFMIHQLMG NGVWHFGETM CTLITAMDAN SQFTSTYILT AMAIDRYLAT VHPISSTKFR K PSVATLVI ...String: QGGTMDLEAS LLPTGPNASN TSDGPDNLTS AGSPPRTGSI SYINIIMPSV FGTICLLGII GNSTVIFAVV KKSKLHWCNN VPDIFIINL SVVDLLFLLG MPFMIHQLMG NGVWHFGETM CTLITAMDAN SQFTSTYILT AMAIDRYLAT VHPISSTKFR K PSVATLVI CLLWALSFIS ITPVWLYARL IPFPGGAVGC GIRLPNPDTD LYWFTLYQFF LAFALPFVVI TAAYVRILQR MT SSVAPAS QRSIRLRTKR VTRTAIAICL VFFVCWAPYY VLQLTQLSIS RPTLTFVYLY NAAISLGYAN SCLNPFVYIV LCE TFRKRL VLSVKPAAQG QLRAGSSGGG GSGGGGSSGV FTLEDFVGDW EQTAAYNLDQ VLEQGGVSSL LQNLAVSVTP IQRI VR UniProtKB: Melanin-concentrating hormone receptor 1 |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.04 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 18.0 µm / Nominal defocus min: 8.0 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.01 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 311033 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |