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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Cryo-EM structure of the DHA bound FFA1-Gq complex | |||||||||
![]() | DHA-FFA1-miniGq | |||||||||
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Function / homology | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Zhang X / Tikhonova I / Milligan G / Zhang C | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis for the ligand recognition and signaling of free fatty acid receptors. Authors: Xuan Zhang / Abdul-Akim Guseinov / Laura Jenkins / Kunpeng Li / Irina G Tikhonova / Graeme Milligan / Cheng Zhang / ![]() ![]() Abstract: Free fatty acid receptors 1 to 4 (FFA1 to FFA4) are class A G protein-coupled receptors (GPCRs). FFA1 to FFA3 share substantial sequence similarity, whereas FFA4 is unrelated. However, FFA1 and FFA4 ...Free fatty acid receptors 1 to 4 (FFA1 to FFA4) are class A G protein-coupled receptors (GPCRs). FFA1 to FFA3 share substantial sequence similarity, whereas FFA4 is unrelated. However, FFA1 and FFA4 are activated by long-chain fatty acids, while FFA2 and FFA3 respond to short-chain fatty acids generated by intestinal microbiota. FFA1, FFA2, and FFA4 are potential drug targets for metabolic and inflammatory conditions. Here, we determined the active structures of FFA1 and FFA4 bound to docosahexaenoic acid, FFA4 bound to the synthetic agonist TUG-891, and butyrate-bound FFA2, each complexed with an engineered heterotrimeric G protein (miniG), by cryo-electron microscopy. Together with computational simulations and mutagenesis studies, we elucidated the similarities and differences in the binding modes of fatty acid ligands to their respective GPCRs. Our findings unveiled distinct mechanisms of receptor activation and G protein coupling. We anticipate that these outcomes will facilitate structure-based drug development and underpin future research on this group of GPCRs. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19 KB 19 KB | Display Display | ![]() |
Images | ![]() | 35.9 KB | ||
Filedesc metadata | ![]() | 6.4 KB | ||
Others | ![]() ![]() | 59.5 MB 59.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8t3vMC ![]() 8t3oC ![]() 8t3qC ![]() 8t3sC 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
File | ![]() | ||||||||||||||||||||
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Annotation | DHA-FFA1-miniGq | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.826 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: DHA-FFA1-miniGq-half B
File | emd_41013_half_map_1.map | ||||||||||||
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Annotation | DHA-FFA1-miniGq-half_B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: DHA-FFA1-miniGq-half A
File | emd_41013_half_map_2.map | ||||||||||||
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Annotation | DHA-FFA1-miniGq-half_A | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : DHA-FFA1-miniGq complex
Entire | Name: DHA-FFA1-miniGq complex |
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Components |
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-Supramolecule #1: DHA-FFA1-miniGq complex
Supramolecule | Name: DHA-FFA1-miniGq complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Guanine nucleotide-binding protein G(q) subunit alpha
Macromolecule | Name: Guanine nucleotide-binding protein G(q) subunit alpha / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 26.569172 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: VSAEDKAAAE RSKMIDKNLR EDGEKARRTL RLLLLGADNS GKSTIVKQMS GIFETKFQVD KVNFHMFDVG GQRDERRKWI QCFNDVTAI IFVVDSSDYN RLQEALNDFK SIWNNRWLRT ISVILFLNKQ DLLAEKVLAG KSKIEDYFPE FARYTTPEDA T PEPGEDPR ...String: VSAEDKAAAE RSKMIDKNLR EDGEKARRTL RLLLLGADNS GKSTIVKQMS GIFETKFQVD KVNFHMFDVG GQRDERRKWI QCFNDVTAI IFVVDSSDYN RLQEALNDFK SIWNNRWLRT ISVILFLNKQ DLLAEKVLAG KSKIEDYFPE FARYTTPEDA T PEPGEDPR VTRAKYFIRK EFVDISTASG DGRHICYPHF TCAVDTENAR RIFNDCKDII LQMNLREYNL V |
-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: 37.516941 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 IWNGSS 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: 6.261229 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: TASIAQARKL VEQLKMEANI DRIKVSKAAA DLMAYCEAHA KEDPLLTPVP ASENPFR 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: ![]() ![]() ![]() |
Molecular weight | Theoretical: 28.634797 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS AGGGGSGGGG SGGGGSADIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...String: VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYYA DTVKGRFTIS RDDPKNTLFL QMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS AGGGGSGGGG SGGGGSADIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL LEENLYFQGA SHHHHHHHH |
-Macromolecule #5: Free fatty acid receptor 1
Macromolecule | Name: Free fatty acid receptor 1 / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 29.395521 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: MDLPPQLSFG LYVAAFALGF PLNVLAIRGA TAHARLRLTP SLVYALNLGC SDLLLTVSLP LKAVEALASG AWPLPASLCP VFAVAHFFP LYAGGGFLAA LSAGRYLGAA FPLGYQAFRR PCYSWGVCAA IWALVLCHLG LVFGLEAPGG WLDHSNTSLG I NTPVNGSP ...String: MDLPPQLSFG LYVAAFALGF PLNVLAIRGA TAHARLRLTP SLVYALNLGC SDLLLTVSLP LKAVEALASG AWPLPASLCP VFAVAHFFP LYAGGGFLAA LSAGRYLGAA FPLGYQAFRR PCYSWGVCAA IWALVLCHLG LVFGLEAPGG WLDHSNTSLG I NTPVNGSP VCLEAWDPAS AGPARFSLSL LLFFLPLAIT AFCYVGCLRA LARSGLTHRR KLRAAWVAGG ALLTLLLCVG PY NASNVAS FLYPNLGGSW RKLGLITGAW SVVLNPLVTG YL UniProtKB: Myosin regulatory light chain LC-2, mantle muscle |
-Macromolecule #6: CHOLESTEROL
Macromolecule | Name: CHOLESTEROL / type: ligand / ID: 6 / Number of copies: 1 / Formula: CLR |
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Molecular weight | Theoretical: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-Macromolecule #7: DOCOSA-4,7,10,13,16,19-HEXAENOIC ACID
Macromolecule | Name: DOCOSA-4,7,10,13,16,19-HEXAENOIC ACID / type: ligand / ID: 7 / Number of copies: 1 / Formula: HXA |
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Molecular weight | Theoretical: 328.488 Da |
Chemical component information | ![]() ChemComp-HXA: |
-Experimental details
-Structure determination
Method | ![]() |
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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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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 61.6 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: NONE |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.39 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 305318 |