[English] 日本語
![](img/lk-miru.gif)
- EMDB-25559: Cryo-EM structure of the extracellular module of the full-length ... -
+
Open data
-
Basic information
Entry | Database: EMDB / ID: EMD-25559 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of the extracellular module of the full-length EGFR L834R bound to EGF. "tips-separated" conformation | |||||||||
![]() | L834R:EGF_sep | |||||||||
![]() |
| |||||||||
Function / homology | ![]() negative regulation of secretion / positive regulation of hyaluronan biosynthetic process / negative regulation of cholesterol efflux / positive regulation of cerebellar granule cell precursor proliferation / cerebellar granule cell precursor proliferation / positive regulation of epithelial tube formation / Wnt receptor activity / regulation of calcium ion import / positive regulation of protein localization to early endosome / regulation of protein localization to cell surface ...negative regulation of secretion / positive regulation of hyaluronan biosynthetic process / negative regulation of cholesterol efflux / positive regulation of cerebellar granule cell precursor proliferation / cerebellar granule cell precursor proliferation / positive regulation of epithelial tube formation / Wnt receptor activity / regulation of calcium ion import / positive regulation of protein localization to early endosome / regulation of protein localization to cell surface / Wnt-protein binding / positive regulation of ubiquitin-dependent protein catabolic process / response to hydroxyisoflavone / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / positive regulation of protein kinase C activity / diterpenoid metabolic process / regulation of receptor signaling pathway via JAK-STAT / Shc-EGFR complex / ovulation cycle / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity / EGFR interacts with phospholipase C-gamma / positive regulation of mucus secretion / response to UV-A / epidermal growth factor binding / PLCG1 events in ERBB2 signaling / tongue development / NFE2L2 regulating tumorigenic genes / midgut development / ERBB2-EGFR signaling pathway / hydrogen peroxide metabolic process / PTK6 promotes HIF1A stabilization / digestive tract morphogenesis / epidermal growth factor receptor binding / morphogenesis of an epithelial fold / ERBB2 Activates PTK6 Signaling / branching morphogenesis of an epithelial tube / intracellular vesicle / Signaling by EGFR / response to cobalamin / transmembrane receptor protein tyrosine kinase activator activity / protein tyrosine kinase activator activity / negative regulation of epidermal growth factor receptor signaling pathway / Signaling by ERBB4 / eyelid development in camera-type eye / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / protein insertion into membrane / cerebral cortex cell migration / ERBB2 Regulates Cell Motility / Respiratory syncytial virus (RSV) attachment and entry / positive regulation of receptor internalization / regulation of JNK cascade / : / PI3K events in ERBB2 signaling / positive regulation of cyclin-dependent protein serine/threonine kinase activity / negative regulation of mitotic cell cycle / hair follicle development / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / MAP kinase kinase kinase activity / embryonic placenta development / mammary gland alveolus development / positive regulation of bone resorption / positive regulation of G1/S transition of mitotic cell cycle / canonical Wnt signaling pathway / positive regulation of DNA binding / GAB1 signalosome / salivary gland morphogenesis / peptidyl-tyrosine autophosphorylation / regulation of peptidyl-tyrosine phosphorylation / positive regulation of phosphorylation / positive regulation of glial cell proliferation / positive regulation of vasoconstriction / Signaling by ERBB2 / cellular response to epidermal growth factor stimulus / positive regulation of endothelial cell proliferation / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / cellular response to cadmium ion / EGFR Transactivation by Gastrin / positive regulation of DNA repair / ERK1 and ERK2 cascade / GRB2 events in ERBB2 signaling / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / positive regulation of endothelial cell migration / transmembrane receptor protein tyrosine kinase activity / SHC1 events in ERBB2 signaling / positive regulation of mitotic nuclear division / positive regulation of synaptic transmission, glutamatergic / cellular response to dexamethasone stimulus / ossification / neurogenesis / regulation of ERK1 and ERK2 cascade / guanyl-nucleotide exchange factor activity / basal plasma membrane / neuron projection morphogenesis / positive regulation of superoxide anion generation / platelet alpha granule lumen / positive regulation of peptidyl-threonine phosphorylation Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.4 Å | |||||||||
![]() | Huang Y / Ognjenovic J / Karandur D / Miller K / Merk A / Subramaniam S / Kuriyan J | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: A molecular mechanism for the generation of ligand-dependent differential outputs by the epidermal growth factor receptor. Authors: Yongjian Huang / Jana Ognjenovic / Deepti Karandur / Kate Miller / Alan Merk / Sriram Subramaniam / John Kuriyan / ![]() ![]() Abstract: The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that couples the binding of extracellular ligands, such as EGF and transforming growth factor-α (TGF-α), to the initiation ...The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that couples the binding of extracellular ligands, such as EGF and transforming growth factor-α (TGF-α), to the initiation of intracellular signaling pathways. EGFR binds to EGF and TGF-α with similar affinity, but generates different signals from these ligands. To address the mechanistic basis of this phenomenon, we have carried out cryo-EM analyses of human EGFR bound to EGF and TGF-α. We show that the extracellular module adopts an ensemble of dimeric conformations when bound to either EGF or TGF-α. The two extreme states of this ensemble represent distinct ligand-bound quaternary structures in which the membrane-proximal tips of the extracellular module are either juxtaposed or separated. EGF and TGF-α differ in their ability to maintain the conformation with the membrane-proximal tips of the extracellular module separated, and this conformation is stabilized preferentially by an oncogenic EGFR mutation. Close proximity of the transmembrane helices at the junction with the extracellular module has been associated previously with increased EGFR activity. Our results show how EGFR can couple the binding of different ligands to differential modulation of this proximity, thereby suggesting a molecular mechanism for the generation of ligand-sensitive differential outputs in this receptor family. | |||||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
-
Downloads & links
-EMDB archive
Map data | ![]() | 62.9 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 13.2 KB 13.2 KB | Display Display | ![]() |
Images | ![]() | 184.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 416.4 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 416 KB | Display | |
Data in XML | ![]() | 6.7 KB | Display | |
Data in CIF | ![]() | 7.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7sz1MC ![]() 7sydC ![]() 7syeC ![]() 7sz0C ![]() 7sz5C ![]() 7sz7C C: citing same article ( M: atomic model generated by this map |
---|---|
Similar structure data |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | L834R:EGF_sep | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.0794 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-
Sample components
-Entire : full-length human EGFR(L834R):EGF complex
Entire | Name: full-length human EGFR(L834R):EGF complex |
---|---|
Components |
|
-Supramolecule #1: full-length human EGFR(L834R):EGF complex
Supramolecule | Name: full-length human EGFR(L834R):EGF complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
---|
-Macromolecule #1: Epidermal growth factor receptor
Macromolecule | Name: Epidermal growth factor receptor / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: receptor protein-tyrosine kinase |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 134.477375 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ LGTFEDHFLS LQRMFNNCEV VLGNLEITYV QRNYDLSFLK TIQEVAGYV LIALNTVERI PLENLQIIRG NMYYENSYAL AVLSNYDANK TGLKELPMRN LQEILHGAVR FSNNPALCNV E SIQWRDIV ...String: MRPSGTAGAA LLALLAALCP ASRALEEKKV CQGTSNKLTQ LGTFEDHFLS LQRMFNNCEV VLGNLEITYV QRNYDLSFLK TIQEVAGYV LIALNTVERI PLENLQIIRG NMYYENSYAL AVLSNYDANK TGLKELPMRN LQEILHGAVR FSNNPALCNV E SIQWRDIV SSDFLSNMSM DFQNHLGSCQ KCDPSCPNGS CWGAGEENCQ KLTKIICAQQ CSGRCRGKSP SDCCHNQCAA GC TGPRESD CLVCRKFRNE ATCKDTCPPL MLYNPTTYQM DVNPEGKYSF GATCVKKCPR NYVVTDHGSC VRACGADSYE MEE DGVRKC KKCEGPCRKV CNGIGIGEFK DSLSINATNI KHFKNCTSIS GDLHILPVAF RGDSFTHTPP LDPQELDILK TVKE ITGFL LIQAWPENRT DLHAFENLEI IRGRTKQHGQ FSLAVVSLNI TSLGLRSLKE ISDGDVIISG NKNLCYANTI NWKKL FGTS GQKTKIISNR GENSCKATGQ VCHALCSPEG CWGPEPRDCV SCRNVSRGRE CVDKCNLLEG EPREFVENSE CIQCHP ECL PQAMNITCTG RGPDNCIQCA HYIDGPHCVK TCPAGVMGEN NTLVWKYADA GHVCHLCHPN CTYGCTGPGL EGCPTNG PK IPSIATGMVG ALLLLLVVAL GIGLFMRRRH IVRKRTLRRL LQERELVEPL TPSGEAPNQA LLRILKETEF KKIKVLGS G AFGTVYKGLW IPEGEKVKIP VAIKELREAT SPKANKEILD EAYVMASVDN PHVCRLLGIC LTSTVQLITQ LMPFGCLLD YVREHKDNIG SQYLLNWCVQ IAKGMNYLED RRLVHRDLAA RNVLVKTPQH VKITDFGRAK LLGAEEKEYH AEGGKVPIKW MALESILHR IYTHQSDVWS YGVTVWELMT FGSKPYDGIP ASEISSILEK GERLPQPPIC TIDVYMIMVK CWMIDADSRP K FRELIIEF SKMARDPQRY LVIQGDERMH LPSPTDSNFY RALMDEEDMD DVVDADEYLI PQQGFFSSPS TSRTPLLSSL SA TSNNSTV ACIDRNGLQS CPIKEDSFLQ RYSSDPTGAL TEDSIDDTFL PVPEYINQSV PKRPAGSVQN PVYHNQPLNP APS RDPHYQ DPHSTAVGNP EYLNTVQPTC VNSTFDSPAH WAQKGSHQIS LDNPDYQQDF FPKEAKPNGI FKGSTAENAE YLRV APQSS EFIGA |
-Macromolecule #2: Epidermal growth factor
Macromolecule | Name: Epidermal growth factor / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 6.229027 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: NSDSECPLSH DGYCLHDGVC MYIEALDKYA CNCVVGYIGE RCQYRDLKWW ELR |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Concentration | 0.5 mg/mL |
---|---|
Buffer | pH: 8 |
Grid | Model: UltrAuFoil R1.2/1.3 / Pretreatment - Type: PLASMA CLEANING |
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
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 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |