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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-23923 | |||||||||
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Title | Cryo-EM structure of 2:2 c-MET/NK1 complex | |||||||||
![]() | Cryo-EM structure of 2:2 c-MET/NK1 complex | |||||||||
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Function / homology | ![]() regulation of p38MAPK cascade / regulation of branching involved in salivary gland morphogenesis by mesenchymal-epithelial signaling / negative regulation of guanyl-nucleotide exchange factor activity / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Uchikawa E / Chen ZM / Xiao GY / Zhang XW / Bai XC | |||||||||
![]() | ![]() Title: Structural basis of the activation of c-MET receptor. Authors: Emiko Uchikawa / Zhiming Chen / Guan-Yu Xiao / Xuewu Zhang / Xiao-Chen Bai / ![]() ![]() Abstract: The c-MET receptor is a receptor tyrosine kinase (RTK) that plays essential roles in normal cell development and motility. Aberrant activation of c-MET can lead to both tumors growth and metastatic ...The c-MET receptor is a receptor tyrosine kinase (RTK) that plays essential roles in normal cell development and motility. Aberrant activation of c-MET can lead to both tumors growth and metastatic progression of cancer cells. C-MET can be activated by either hepatocyte growth factor (HGF), or its natural isoform NK1. Here, we report the cryo-EM structures of c-MET/HGF and c-MET/NK1 complexes in the active state. The c-MET/HGF complex structure reveals that, by utilizing two distinct interfaces, one HGF molecule is sufficient to induce a specific dimerization mode of c-MET for receptor activation. The binding of heparin as well as a second HGF to the 2:1 c-MET:HGF complex further stabilize this active conformation. Distinct to HGF, NK1 forms a stable dimer, and bridges two c-METs in a symmetrical manner for activation. Collectively, our studies provide structural insights into the activation mechanisms of c-MET, and reveal how two isoforms of the same ligand use dramatically different mechanisms to activate the receptor. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 70.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 13.1 KB 13.1 KB | Display Display | ![]() |
Images | ![]() | 118.2 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7mobMC ![]() 7mo7C ![]() 7mo8C ![]() 7mo9C ![]() 7moaC C: citing same article ( M: atomic model generated by this map |
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Similar structure data |
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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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Annotation | Cryo-EM structure of 2:2 c-MET/NK1 complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
-Entire : 2:2 c-MET/NK1 complex
Entire | Name: 2:2 c-MET/NK1 complex |
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Components |
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-Supramolecule #1: 2:2 c-MET/NK1 complex
Supramolecule | Name: 2:2 c-MET/NK1 complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() ![]() |
-Macromolecule #1: Hepatocyte growth factor
Macromolecule | Name: Hepatocyte growth factor / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 24.19915 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MWVTKLLPAL LLQHVLLHLL LLPIAIPYAE GQRKRRNTIH EFKKSAKTTL IKIDPALKIK TKKVNTADQC ANRCTRNKGL PFTCKAFVF DKARKQCLWF PFNSMSSGVK KEFGHEFDLY ENKDYIRNCI IGKGRSYKGT VSITKSGIKC QPWSSMIPHE H SFLPSSYR ...String: MWVTKLLPAL LLQHVLLHLL LLPIAIPYAE GQRKRRNTIH EFKKSAKTTL IKIDPALKIK TKKVNTADQC ANRCTRNKGL PFTCKAFVF DKARKQCLWF PFNSMSSGVK KEFGHEFDLY ENKDYIRNCI IGKGRSYKGT VSITKSGIKC QPWSSMIPHE H SFLPSSYR GKDLQENYCR NPRGEEGGPW CFTSNPEVRY EVCDIPQCSE VE |
-Macromolecule #2: Hepatocyte growth factor receptor
Macromolecule | Name: Hepatocyte growth factor receptor / type: protein_or_peptide / ID: 2 / Number of copies: 2 / Enantiomer: LEVO / EC number: ![]() |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 155.720625 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MKAPAVLAPG ILVLLFTLVQ RSNGECKEAL AKSEMNVNMK YQLPNFTAET PIQNVILHEH HIFLGATNYI YVLNEEDLQK VAEYKTGPV LEHPDCFPCQ DCSSKANLSG GVWKDNINMA LVVDTYYDDQ LISCGSVNRG TCQRHVFPHN HTADIQSEVH C IFSPQIEE ...String: MKAPAVLAPG ILVLLFTLVQ RSNGECKEAL AKSEMNVNMK YQLPNFTAET PIQNVILHEH HIFLGATNYI YVLNEEDLQK VAEYKTGPV LEHPDCFPCQ DCSSKANLSG GVWKDNINMA LVVDTYYDDQ LISCGSVNRG TCQRHVFPHN HTADIQSEVH C IFSPQIEE PSQCPDCVVS ALGAKVLSSV KDRFINFFVG NTINSSYFPD HPLHSISVRR LKETKDGFMF LTDQSYIDVL PE FRDSYPI KYVHAFESNN FIYFLTVQRE TLDAQTFHTR IIRFCSINSG LHSYMEMPLE CILTEKRKKR STKKEVFNIL QAA YVSKPG AQLARQIGAS LNDDILFGVF AQSKPDSAEP MDRSAMCAFP IKYVNDFFNK IVNKNNVRCL QHFYGPNHEH CFNR TLLRN SSGCEARRDE YRTEFTTALQ RVDLFMGQFS EVLLTSISTF IKGDLTIANL GTSEGRFMQV VVSRSGPSTP HVNFL LDSH PVSPEVIVEH TLNQNGYTLV ITGKKITKIP LNGLGCRHFQ SCSQCLSAPP FVQCGWCHDK CVRSEECLSG TWTQQI CLP AIYKVFPNSA PLEGGTRLTI CGWDFGFRRN NKFDLKKTRV LLGNESCTLT LSESTMNTLK CTVGPAMNKH FNMSIII SN GHGTTQYSTF SYVDPVITSI SPKYGPMAGG TLLTLTGNYL NSGNSRHISI GGKTCTLKSV SNSILECYTP AQTISTEF A VKLKIDLANR ETSIFSYRED PIVYEIHPTK SFISGGSTIT GVGKNLNSVS VPRMVINVHE AGRNFTVACQ HRSNSEIIC CTTPSLQQLN LQLPLKTKAF FMLDGILSKY FDLIYVHNPV FKPFEKPVMI SMGNENVLEI KGNDIDPEAV KGEVLKVGNK SCENIHLHS EAVLCTVPND LLKLNSELNI EWKQAISSTV LGKVIVQPDQ NFTGLIAGVV SISTALLLLL GFFLWLKKRK Q IKDLGSEL VRYDARVHTP HLDRLVSARS VSPTTEMVSN ESVDYRATFP EDQFPNSSQN GSCRQVQYPL TDMSPILTSG DS DISSPLL QNTVHIDLSA LNPELVQAVQ HVVIGPSSLI VHFNEVIGRG HFGCVYHGTL LDNDGKKIHC AVKSLNRITD IGE VSQFLT EGIIMKDFSH PNVLSLLGIC LRSEGSPLVV LPYMKHGDLR NFIRNETHNP TVKDLIGFGL QVAKGMKYLA SKKF VHRDL AARNCMLDEK FTVKVADFGL ARDMYDKEYY SVHNKTGAKL PVKWMALESL QTQKFTTKSD VWSFGVLLWE LMTRG APPY PDVNTFDITV YLLQGRRLLQ PEYCPDPLYE VMLKCWHPKA EMRPSFSELV SRISAIFSTF IGEHYVHVNA TYVNVK CVA PYPSLLSSED NADDEVDTRP ASFWETS |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Initial angle assignment | Type: PROJECTION MATCHING / Software - Name: RELION |
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Final 3D classification | Software - Name: RELION |
Final angle assignment | Type: PROJECTION MATCHING / Software - Name: RELION |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 5.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 11570 |