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- EMDB-33585: Cryo-EM structure of the octreotide-bound SSTR2-miniGo-scFv16 complex -
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Open data
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Basic information
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Title | Cryo-EM structure of the octreotide-bound SSTR2-miniGo-scFv16 complex | |||||||||
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Function / homology | ![]() somatostatin receptor activity / peristalsis / neuropeptide binding / vesicle docking involved in exocytosis / cellular response to glucocorticoid stimulus / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / response to starvation / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / mu-type opioid receptor binding ...somatostatin receptor activity / peristalsis / neuropeptide binding / vesicle docking involved in exocytosis / cellular response to glucocorticoid stimulus / G protein-coupled dopamine receptor signaling pathway / regulation of heart contraction / response to starvation / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / neuropeptide signaling pathway / negative regulation of insulin secretion / G protein-coupled serotonin receptor binding / forebrain development / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / cerebellum development / locomotory behavior / muscle contraction / cellular response to estradiol stimulus / PDZ domain binding / 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 / 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 / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / cell body / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / spermatogenesis / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / neuron projection / G protein-coupled receptor signaling pathway / negative regulation of cell population proliferation / lysosomal membrane / GTPase activity / synapse / dendrite / 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: 3.25 Å | |||||||||
![]() | Chen S / Zheng S | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular basis for the selective G protein signaling of somatostatin receptors. Authors: Sijia Chen / Xiao Teng / Sanduo Zheng / ![]() Abstract: G protein-coupled receptors (GPCRs) modulate every aspect of physiological functions mainly through activating heterotrimeric G proteins. A majority of GPCRs promiscuously couple to multiple G ...G protein-coupled receptors (GPCRs) modulate every aspect of physiological functions mainly through activating heterotrimeric G proteins. A majority of GPCRs promiscuously couple to multiple G protein subtypes. Here we validate that in addition to the well-known G pathway, somatostatin receptor 2 and 5 (SSTR2 and SSTR5) couple to the G pathway and show that smaller ligands preferentially activate the G pathway. We further determined cryo-electron microscopy structures of the SSTR2‒G and SSTR2‒G complexes bound to octreotide and SST-14. Structural and functional analysis revealed that G protein selectivity of SSTRs is not only determined by structural elements in the receptor-G protein interface, but also by the conformation of the agonist-binding pocket. Accordingly, smaller ligands fail to stabilize a broader agonist-binding pocket of SSTRs that is required for efficient G coupling but not G coupling. Our studies facilitate the design of drugs with selective G protein signaling to improve therapeutic efficacy. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 20.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 20.5 KB 20.5 KB | Display Display | ![]() |
Images | ![]() | 26.5 KB | ||
Others | ![]() ![]() | 20.6 MB 20.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 650.5 KB | Display | ![]() |
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Full document | ![]() | 650.1 KB | Display | |
Data in XML | ![]() | 10.1 KB | Display | |
Data in CIF | ![]() | 11.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7y24MC ![]() 7y26C ![]() 7y27C 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
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Voxel size | X=Y=Z: 1.087 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_33585_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_33585_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
+Entire : complex of SSTR2-miniGo-scFv16 bound with octreotide
+Supramolecule #1: complex of SSTR2-miniGo-scFv16 bound with octreotide
+Supramolecule #2: G(o) subunit alpha
+Supramolecule #3: G(I)/G(S)/G(T) subunit beta-1, G(I)/G(S)/G(O) subunit gamma-2
+Supramolecule #4: svFv16, octreotide
+Supramolecule #5: Somatostatin receptor type 2
+Macromolecule #1: Guanine nucleotide-binding protein G(o) subunit alpha
+Macromolecule #2: 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 #4: single Fab chain (svFv16)
+Macromolecule #5: Octreotide
+Macromolecule #6: Somatostatin receptor type 2
-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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Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD |
Vitrification | Cryogen name: ETHANE |
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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: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 5.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.25 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 687989 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |