[English] 日本語
![](img/lk-miru.gif)
- EMDB-33871: Cryo-EM structure of the INSL5-bound human relaxin family peptide... -
+
Open data
-
Basic information
Entry | ![]() | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of the INSL5-bound human relaxin family peptidereceptor 4 (RXFP4)-Gi complex | ||||||||||||||||||||||||||||||||||||
![]() | |||||||||||||||||||||||||||||||||||||
![]() |
| ||||||||||||||||||||||||||||||||||||
Function / homology | ![]() Relaxin receptors / positive regulation of feeding behavior / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / positive regulation of urine volume / Activation of the phototransduction cascade ...Relaxin receptors / positive regulation of feeding behavior / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway involved in heart process / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / G protein-coupled adenosine receptor signaling pathway / negative regulation of calcium ion-dependent exocytosis / positive regulation of urine volume / Activation of the phototransduction cascade / negative regulation of adenylate cyclase activity / G protein-coupled peptide receptor activity / positive regulation of neural precursor cell proliferation / gamma-aminobutyric acid signaling pathway / negative regulation of synaptic transmission / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / neuronal dense core vesicle / regulation of calcium ion transport / negative regulation of apoptotic signaling pathway / neuropeptide signaling pathway / Adenylate cyclase inhibitory pathway / positive regulation of insulin receptor signaling pathway / positive regulation of vascular associated smooth muscle cell proliferation / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to nutrient / positive regulation of superoxide anion generation / Regulation of insulin secretion / G protein-coupled receptor binding / G-protein beta/gamma-subunit complex binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / hormone activity / ADP signalling through P2Y purinoceptor 12 / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / GPER1 signaling / G-protein beta-subunit binding / heterotrimeric G-protein complex / extracellular vesicle / signaling receptor complex adaptor activity / midbody / G alpha (i) signalling events / cell body / G alpha (s) signalling events / cell population proliferation / Extra-nuclear estrogen signaling / positive regulation of ERK1 and ERK2 cascade / positive regulation of cell migration / G protein-coupled receptor signaling pathway / cell division / GTPase activity / centrosome / synapse / dendrite / positive regulation of cell population proliferation / GTP binding / signal transduction / extracellular exosome / extracellular region / nucleoplasm / membrane / metal ion binding / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||||||||||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() | ||||||||||||||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.19 Å | ||||||||||||||||||||||||||||||||||||
![]() | Chen Y / Zhou QT / Wang J / Xu YW / Wang Y / Yan JH / Wang YB / Zhu Q / Zhao FH / Li CH ...Chen Y / Zhou QT / Wang J / Xu YW / Wang Y / Yan JH / Wang YB / Zhu Q / Zhao FH / Li CH / Chen CW / Cai XQ / Bathgate RAD / Shen C / Liu H / Xu HE / Yang DH / Wang MW | ||||||||||||||||||||||||||||||||||||
Funding support | ![]()
| ||||||||||||||||||||||||||||||||||||
![]() | ![]() Title: Ligand recognition mechanism of the human relaxin family peptide receptor 4 (RXFP4). Authors: Yan Chen / Qingtong Zhou / Jiang Wang / Youwei Xu / Yun Wang / Jiahui Yan / Yibing Wang / Qi Zhu / Fenghui Zhao / Chenghao Li / Chuan-Wei Chen / Xiaoqing Cai / Ross A D Bathgate / Chun Shen ...Authors: Yan Chen / Qingtong Zhou / Jiang Wang / Youwei Xu / Yun Wang / Jiahui Yan / Yibing Wang / Qi Zhu / Fenghui Zhao / Chenghao Li / Chuan-Wei Chen / Xiaoqing Cai / Ross A D Bathgate / Chun Shen / H Eric Xu / Dehua Yang / Hong Liu / Ming-Wei Wang / ![]() ![]() ![]() Abstract: Members of the insulin superfamily regulate pleiotropic biological processes through two types of target-specific but structurally conserved peptides, insulin/insulin-like growth factors and ...Members of the insulin superfamily regulate pleiotropic biological processes through two types of target-specific but structurally conserved peptides, insulin/insulin-like growth factors and relaxin/insulin-like peptides. The latter bind to the human relaxin family peptide receptors (RXFPs). Here, we report three cryo-electron microscopy structures of RXFP4-G protein complexes in the presence of the endogenous ligand insulin-like peptide 5 (INSL5) or one of the two small molecule agonists, compound 4 and DC591053. The B chain of INSL5 adopts a single α-helix that penetrates into the orthosteric pocket, while the A chain sits above the orthosteric pocket, revealing a peptide-binding mode previously unknown. Together with mutagenesis and functional analyses, the key determinants responsible for the peptidomimetic agonism and subtype selectivity were identified. Our findings not only provide insights into ligand recognition and subtype selectivity among class A G protein-coupled receptors, but also expand the knowledge of signaling mechanisms in the insulin superfamily. | ||||||||||||||||||||||||||||||||||||
History |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 59.7 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 25.8 KB 25.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 9.1 KB | Display | ![]() |
Images | ![]() | 77 KB | ||
Others | ![]() ![]() | 59.3 MB 59.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7yj4MC ![]() 7yk6C ![]() 7yk7C 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 | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.071 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: #2
File | emd_33871_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_33871_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
+Entire : Cryo-EM structure of the human relaxin family peptide receptor 4 ...
+Supramolecule #1: Cryo-EM structure of the human relaxin family peptide receptor 4 ...
+Supramolecule #2: INSL5
+Supramolecule #3: human relaxin family peptide receptor 4
+Supramolecule #4: G protein
+Supramolecule #5: scFv16
+Macromolecule #1: Insulin-like peptide INSL5 A chain
+Macromolecule #2: Insulin-like peptide INSL5 B chain
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #4: Guanine nucleotide-binding protein G(i) subunit alpha-2
+Macromolecule #5: Relaxin-3 receptor 2
+Macromolecule #6: scFv16
+Macromolecule #7: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 7.4 |
---|---|
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 80.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: OTHER |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |