+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | GPR21 wt with G15 complex | |||||||||
![]() | map | |||||||||
![]() |
| |||||||||
Function / homology | ![]() positive regulation of multicellular organism growth / PKA activation in glucagon signalling / hair follicle placode formation / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / intracellular transport / D1 dopamine receptor binding / Hedgehog 'off' state / beta-2 adrenergic receptor binding ...positive regulation of multicellular organism growth / PKA activation in glucagon signalling / hair follicle placode formation / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / intracellular transport / D1 dopamine receptor binding / Hedgehog 'off' state / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / negative regulation of insulin receptor signaling pathway / trans-Golgi network membrane / G protein-coupled receptor activity / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / G-protein beta/gamma-subunit complex binding / bone development / 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 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 / cognition / 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 / platelet aggregation / 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 / sensory perception of smell / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / insulin receptor signaling pathway / GTPase binding / glucose homeostasis / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / positive regulation of cold-induced thermogenesis / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
![]() | Chen BO | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: Cryo-EM structures of orphan GPR21 signaling complexes. Authors: Xi Lin / Bo Chen / Yiran Wu / Yingqi Han / Ao Qi / Junyan Wang / Zhao Yang / Xiaohu Wei / Tingting Zhao / Lijie Wu / Xin Xie / Jinpeng Sun / Jie Zheng / Suwen Zhao / Fei Xu / ![]() Abstract: GPR21 is a class-A orphan G protein-coupled receptor (GPCR) and a potential therapeutic target for type 2 diabetes and other metabolic disorders. This receptor shows high basal activity in coupling ...GPR21 is a class-A orphan G protein-coupled receptor (GPCR) and a potential therapeutic target for type 2 diabetes and other metabolic disorders. This receptor shows high basal activity in coupling to multiple G proteins in the absence of any known endogenous agonist or synthetic ligand. Here, we present the structures of ligand-free human GPR21 bound to heterotrimeric miniGs and miniG15 proteins, respectively. We identified an agonist-like motif in extracellular loop 2 (ECL2) that occupies the orthosteric pocket and promotes receptor activation. A side pocket that may be employed as a new ligand binding site was also uncovered. Remarkably, G protein binding is accommodated by a flexible cytoplasmic portion of transmembrane helix 6 (TM6) which adopts little or undetectable outward movement. These findings will enable the design of modulators for GPR21 for understanding its signal transduction and exploring opportunity for deorphanization. | |||||||||
History |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 2.6 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 18.3 KB 18.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.2 KB | Display | ![]() |
Images | ![]() | 47.3 KB | ||
Others | ![]() ![]() | 49.8 MB 49.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 612.8 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 612.4 KB | Display | |
Data in XML | ![]() | 16.1 KB | Display | |
Data in CIF | ![]() | 21.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8hj2MC ![]() 8hixC ![]() 8hj0C ![]() 8hj1C M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.832 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: half1
File | emd_33481_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half1 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half2
File | emd_33481_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half2 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : GPR21(wt) with G15
Entire | Name: GPR21(wt) with G15 |
---|---|
Components |
|
-Supramolecule #1: GPR21(wt) with G15
Supramolecule | Name: GPR21(wt) with G15 / type: complex / ID: 1 / Chimera: Yes / Parent: 0 / Macromolecule list: all |
---|---|
Source (natural) | Organism: ![]() |
-Macromolecule #1: 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: 1 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 37.41693 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...String: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN |
-Macromolecule #2: 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: 2 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 10.366764 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: HHHHHHGGGS DSLEFIASKL AGGGSMASNN TASIAQARKL VEQLKMEANI DRIKVSKAAA DLMAYCEAHA KEDPLLTPVP ASENPFREK KFFSAIL |
-Macromolecule #3: Nb35
Macromolecule | Name: Nb35 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 16.054232 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MKYLLPTAAA GLLLLAAQPA MAMQVQLQES GGGLVQPGGS LRLSCAASGF TFSNYKMNWV RQAPGKGLEW VSDISQSGAS ISYTGSVKG RFTISRDNAK NTLYLQMNSL KPEDTAVYYC ARCPAPFTRD CFDVTSTTYA YRGQGTQVTV |
-Macromolecule #4: Probable G-protein coupled receptor 21
Macromolecule | Name: Probable G-protein coupled receptor 21 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 39.545992 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MNSTLDGNQS SHPFCLLAFG YLETVNFCLL EVLIIVFLTV LIISGNIIVI FVFHCAPLLN HHTTSYFIQT MAYADLFVGV SCVVPSLSL LHHPLPVEES LTCQIFGFVV SVLKSVSMAS LACISIDRYI AITKPLTYNT LVTPWRLRLC IFLIWLYSTL V FLPSFFHW ...String: MNSTLDGNQS SHPFCLLAFG YLETVNFCLL EVLIIVFLTV LIISGNIIVI FVFHCAPLLN HHTTSYFIQT MAYADLFVGV SCVVPSLSL LHHPLPVEES LTCQIFGFVV SVLKSVSMAS LACISIDRYI AITKPLTYNT LVTPWRLRLC IFLIWLYSTL V FLPSFFHW GKPGYHGDVF QWCAESWHTD SYFTLFIVMM LYAPAALIVC FTYFNIFRIC QQHTKDISER QARFSSQSGE TG EVQACPD KRYAMVLFRI TSVFYILWLP YIIYFLLESS TGHSNRFASF LTTWLAISNS FCNCVIYSLS NSVFQRGLKR LSG AMCTSC ASQTTANDPY TVRSKGPLNG CHI |
-Macromolecule #5: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Macromolecule | Name: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 28.768418 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: GNSKTEDQRN EEKAQREANK KIEKQLQKDK QVYRATHRLL LLGADNSGKS TIVKQMRILH GGSGGSGGTS GIFETKFQVD KVNFHMFDV GGQRDERRKW IQCFNDVTAI IFVVDSSDYN RLQEALNLFK SIWNNRWLRT ISVILFLNKQ DLLAEKVLAG K SKIEDYFP ...String: GNSKTEDQRN EEKAQREANK KIEKQLQKDK QVYRATHRLL LLGADNSGKS TIVKQMRILH GGSGGSGGTS GIFETKFQVD KVNFHMFDV GGQRDERRKW IQCFNDVTAI IFVVDSSDYN RLQEALNLFK SIWNNRWLRT ISVILFLNKQ DLLAEKVLAG K SKIEDYFP EFARYTTPED ATPEPGEDPR VTRAKYFIRD EFLRISTASG DGRHYCYPHF TCAVDTENAR RIFNDCRDSV LA RYLDEIN LL |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 7 |
---|---|
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 0.7000000000000001 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |