[English] 日本語
Yorodumi- EMDB-33304: CryoEM structure of somatostatin receptor 4 (SSTR4) with Gi1 and ... -
+
Open data
-
Basic information
| Entry | ![]() | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Title | CryoEM structure of somatostatin receptor 4 (SSTR4) with Gi1 and J-2156 | |||||||||||||||||||||||||||
Map data | ||||||||||||||||||||||||||||
Sample |
| |||||||||||||||||||||||||||
Keywords | G protein-coupled receptor / somatostatin receptor 2 / cryo-EM / STRUCTURAL PROTEIN | |||||||||||||||||||||||||||
| Function / homology | Function and homology informationsomatostatin receptor activity / neuropeptide binding / cellular response to glucocorticoid stimulus / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / regulation of eating behavior / adenylate cyclase inhibitor activity / T cell migration / positive regulation of protein localization to cell cortex / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway ...somatostatin receptor activity / neuropeptide binding / cellular response to glucocorticoid stimulus / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / regulation of eating behavior / adenylate cyclase inhibitor activity / T cell migration / positive regulation of protein localization to cell cortex / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / cellular response to forskolin / regulation of mitotic spindle organization / Peptide ligand-binding receptors / mast cell degranulation / chemokine-mediated signaling pathway / neuropeptide signaling pathway / Regulation of insulin secretion / response to prostaglandin E / positive regulation of cholesterol biosynthetic process / G protein-coupled receptor binding / response to peptide hormone / G-protein beta/gamma-subunit complex binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / GDP binding / G beta:gamma signalling through BTK / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / G alpha (12/13) signalling events / G-protein beta-subunit binding / extracellular vesicle / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / GTPase binding / G protein activity / midbody / Ca2+ pathway / cell cortex / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / ciliary basal body / G alpha (s) signalling events / G alpha (q) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / Ras protein signal transduction / Extra-nuclear estrogen signaling / neuron projection / G protein-coupled receptor signaling pathway / negative regulation of cell population proliferation / cell division / lysosomal membrane / GTPase activity / centrosome / synapse / GTP binding / protein-containing complex binding / magnesium ion binding / signal transduction / extracellular exosome / membrane / nucleus / plasma membrane / cytosol / cytoplasm Similarity search - Function | |||||||||||||||||||||||||||
| Biological species | Homo sapiens (human) / ![]() | |||||||||||||||||||||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 2.8 Å | |||||||||||||||||||||||||||
Authors | Wenli Z / Shuo H / Na Q / Wenbo Z / Mengjie L / Dehua Y / Ming-Wei W / Wu B / Zhao Q | |||||||||||||||||||||||||||
| Funding support | China, 8 items
| |||||||||||||||||||||||||||
Citation | Journal: Cell Res / Year: 2022Title: Structural insights into ligand recognition and selectivity of somatostatin receptors. Authors: Wenli Zhao / Shuo Han / Na Qiu / Wenbo Feng / Mengjie Lu / Wenru Zhang / Mu Wang / Qingtong Zhou / Shutian Chen / Wei Xu / Juan Du / Xiaojing Chu / Cuiying Yi / Antao Dai / Liaoyuan Hu / ...Authors: Wenli Zhao / Shuo Han / Na Qiu / Wenbo Feng / Mengjie Lu / Wenru Zhang / Mu Wang / Qingtong Zhou / Shutian Chen / Wei Xu / Juan Du / Xiaojing Chu / Cuiying Yi / Antao Dai / Liaoyuan Hu / Michelle Y Shen / Yaping Sun / Qing Zhang / Yingli Ma / Wenge Zhong / Dehua Yang / Ming-Wei Wang / Beili Wu / Qiang Zhao / ![]() Abstract: Somatostatin receptors (SSTRs) play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone, and thus are considered as targets for ...Somatostatin receptors (SSTRs) play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone, and thus are considered as targets for treating multiple tumors. Despite great progress made in therapeutic development against this diverse receptor family, drugs that target SSTRs still show limited efficacy with preferential binding affinity and conspicuous side-effects. Here, we report five structures of SSTR2 and SSTR4 in different states, including two crystal structures of SSTR2 in complex with a selective peptide antagonist and a non-peptide agonist, respectively, a cryo-electron microscopy (cryo-EM) structure of G-bound SSTR2 in the presence of the endogenous ligand SST-14, as well as two cryo-EM structures of G-bound SSTR4 in complex with SST-14 and a small-molecule agonist J-2156, respectively. By comparison of the SSTR structures in different states, molecular mechanisms of agonism and antagonism were illustrated. Together with computational and functional analyses, the key determinants responsible for ligand recognition and selectivity of different SSTR subtypes and multiform binding modes of peptide and non-peptide ligands were identified. Insights gained in this study will help uncover ligand selectivity of various SSTRs and accelerate the development of new molecules with better efficacy by targeting SSTRs. | |||||||||||||||||||||||||||
| History |
|
-
Structure visualization
| Supplemental images |
|---|
-
Downloads & links
-EMDB archive
| Map data | emd_33304.map.gz | 59.7 MB | EMDB map data format | |
|---|---|---|---|---|
| Header (meta data) | emd-33304-v30.xml emd-33304.xml | 21.6 KB 21.6 KB | Display Display | EMDB header |
| Images | emd_33304.png | 72.3 KB | ||
| Filedesc metadata | emd-33304.cif.gz | 6.7 KB | ||
| Others | emd_33304_half_map_1.map.gz emd_33304_half_map_2.map.gz | 49.7 MB 49.7 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33304 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33304 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 7xmtMC ![]() 7xmrC ![]() 7xmsC ![]() 7xn9C ![]() 7xnaC M: atomic model generated by this map C: citing same article ( |
|---|---|
| Similar structure data | Similarity search - Function & homology F&H Search |
-
Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
|---|---|
| Related items in Molecule of the Month |
-
Map
| File | Download / File: emd_33304.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 1.045 Å | ||||||||||||||||||||||||||||||||||||
| Density |
| ||||||||||||||||||||||||||||||||||||
| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
|
-Supplemental data
-Half map: #2
| File | emd_33304_half_map_1.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & Slices |
| ||||||||||||
| Density Histograms |
-Half map: #1
| File | emd_33304_half_map_2.map | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Projections & Slices |
| ||||||||||||
| Density Histograms |
-
Sample components
-Entire : Complex structure of somatostatin receptor 4 (SSTR4) with Gi and ...
| Entire | Name: Complex structure of somatostatin receptor 4 (SSTR4) with Gi and J-2156 |
|---|---|
| Components |
|
-Supramolecule #1: Complex structure of somatostatin receptor 4 (SSTR4) with Gi and ...
| Supramolecule | Name: Complex structure of somatostatin receptor 4 (SSTR4) with Gi and J-2156 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#5 |
|---|---|
| Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Somatostatin receptor type 4
| Macromolecule | Name: Somatostatin receptor type 4 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 40.667375 KDa |
| Recombinant expression | Organism: Insecta environmental sample (insect) |
| Sequence | String: DYKDDDDGAP SAPSTLPPGG EEGLGTAWPS AANASSAPAE AEEAVAGPGD ARAAGMVAIQ CIYALVCLVG LVGNALVIFV ILRYAKMKT ATNIYLLNLA VADELFMLSV PFVASSAALR HWPFGSVLCR AVLSVDGLNM FTSVFCLTVL SVDRYVAVVH P LRAATYRR ...String: DYKDDDDGAP SAPSTLPPGG EEGLGTAWPS AANASSAPAE AEEAVAGPGD ARAAGMVAIQ CIYALVCLVG LVGNALVIFV ILRYAKMKT ATNIYLLNLA VADELFMLSV PFVASSAALR HWPFGSVLCR AVLSVDGLNM FTSVFCLTVL SVDRYVAVVH P LRAATYRR PSVAKLINLG VWLASLLVTL PIAIFADTRP ARGGQAVACN LQWPHPAWSA VFVVYTFLLG FLLPVLAIGL CY LLIVGKM RAVALRAGWQ QRRRSEKKIT RLVLMFVVVF VLCWMPFYVV QLLNLFVTSL DATVNHVSLI LSYANSCANP ILY GFLSDN FRRFFQRVLC LEFLEVLFQG PWSHPQFEKG GGSGGGSGGS AWSHPQFEK UniProtKB: Somatostatin receptor type 4 |
-Macromolecule #2: 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: 2 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 40.447141 KDa |
| Recombinant expression | Organism: Insecta environmental sample (insect) |
| Sequence | String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKCTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKCTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVTAQRSER 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 #3: single chain variable fragment of antibody
| Macromolecule | Name: single chain variable fragment of antibody / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: ![]() |
| Molecular weight | Theoretical: 31.549107 KDa |
| Recombinant expression | Organism: Insecta environmental sample (insect) |
| Sequence | String: MKTIIALSYI FCLVFADYKD DDDGAPSEPD VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS SGGGGSGGGG S GGGGSDIV ...String: MKTIIALSYI FCLVFADYKD DDDGAPSEPD VQLVESGGGL VQPGGSRKLS CSASGFAFSS FGMHWVRQAP EKGLEWVAYI SSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSED TAMYYCVRSI YYYGSSPFDF WGQGTTLTVS SGGGGSGGGG S GGGGSDIV MTQATSSVPV TPGESVSISC RSSKSLLHSN GNTYLYWFLQ RPGQSPQLLI YRMSNLASGV PDRFSGSGSG TA FTLTISR LEAEDVGVYY CMQHLEYPLT FGAGTKLELE FLEVLFQGPH HHHHH |
-Macromolecule #4: 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: 4 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 7.861143 KDa |
| Recombinant expression | Organism: Insecta environmental sample (insect) |
| 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 #5: 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: 5 / Number of copies: 1 / Enantiomer: LEVO |
|---|---|
| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 38.744371 KDa |
| Recombinant expression | Organism: Insecta environmental sample (insect) |
| 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 LKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-Macromolecule #6: (2~{S})-2-[[(2~{S})-4-azanyl-2-[(4-methylnaphthalen-1-yl)sulfonyl...
| Macromolecule | Name: (2~{S})-2-[[(2~{S})-4-azanyl-2-[(4-methylnaphthalen-1-yl)sulfonylamino]butanoyl]amino]-3-phenyl-propanimidic acid type: ligand / ID: 6 / Number of copies: 1 / Formula: I8B |
|---|---|
| Molecular weight | Theoretical: 468.569 Da |
| Chemical component information | ![]() ChemComp-I8B: |
-Experimental details
-Structure determination
| Method | cryo EM |
|---|---|
Processing | single particle reconstruction |
| Aggregation state | particle |
-
Sample preparation
| Buffer | pH: 7.5 |
|---|---|
| Grid | Material: NICKEL/TITANIUM |
| 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: 70.0 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: 2.3000000000000003 µm / Nominal defocus min: 1.3 µm |
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
-
Image processing
| Startup model | Type of model: INSILICO MODEL |
|---|---|
| Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.8 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 600908 |
| Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
| Final angle assignment | Type: MAXIMUM LIKELIHOOD |
Movie
Controller
About Yorodumi



Keywords
Homo sapiens (human)
Authors
China, 8 items
Citation




































Z (Sec.)
Y (Row.)
X (Col.)




































Insecta environmental sample (insect)
FIELD EMISSION GUN
