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- EMDB-10615: FAK structure from single particle analysis of 2D crystals -

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Basic information

Entry
Database: EMDB / ID: EMD-10615
TitleFAK structure from single particle analysis of 2D crystals
Map dataMap obtained from single particle analysis of FAK 2D crystals.
Sample
  • Complex: Focal adhesion kinase
    • Protein or peptide: Focal adhesion kinase 1
KeywordsKinase / Focal Adhesion / Membrane / CELL ADHESION
Function / homology
Function and homology information


Apoptotic cleavage of cellular proteins / NCAM signaling for neurite out-growth / RAF/MAP kinase cascade / RHO GTPases Activate WASPs and WAVEs / Regulation of actin dynamics for phagocytic cup formation / radial glia-guided pyramidal neuron migration / negative regulation of protein autophosphorylation / calcium-dependent cysteine-type endopeptidase activity / positive regulation of substrate-dependent cell migration, cell attachment to substrate / Integrin signaling ...Apoptotic cleavage of cellular proteins / NCAM signaling for neurite out-growth / RAF/MAP kinase cascade / RHO GTPases Activate WASPs and WAVEs / Regulation of actin dynamics for phagocytic cup formation / radial glia-guided pyramidal neuron migration / negative regulation of protein autophosphorylation / calcium-dependent cysteine-type endopeptidase activity / positive regulation of substrate-dependent cell migration, cell attachment to substrate / Integrin signaling / GRB2:SOS provides linkage to MAPK signaling for Integrins / DCC mediated attractive signaling / MET activates PTK2 signaling / Extra-nuclear estrogen signaling / EPHB-mediated forward signaling / p130Cas linkage to MAPK signaling for integrins / VEGFA-VEGFR2 Pathway / angiogenesis involved in wound healing / signal complex assembly / response to pH / negative regulation of cell-substrate adhesion / wound healing, spreading of cells / positive regulation of focal adhesion assembly / positive regulation of protein tyrosine kinase activity / negative regulation of anoikis / regulation of cell adhesion / response to muscle stretch / ciliary basal body / molecular function activator activity / actin filament organization / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / epidermal growth factor receptor signaling pathway / sarcolemma / integrin binding / positive regulation of protein binding / cell cortex / protease binding / protein tyrosine kinase activity / protein autophosphorylation / dendritic spine / positive regulation of cell migration / focal adhesion / centrosome / positive regulation of cell population proliferation / perinuclear region of cytoplasm / ATP binding / identical protein binding / nucleus / plasma membrane / cytoplasm
Similarity search - Function
Focal adhesion kinase, targeting (FAT) domain / Focal adhesion kinase, targeting (FAT) domain superfamily / Focal adhesion kinase, N-terminal / FAK1/PYK2, FERM domain C-lobe / Focal adhesion targeting region / FERM N-terminal domain / : / FAK1/PYK2, FERM domain C-lobe / FERM domain signature 2. / FERM central domain ...Focal adhesion kinase, targeting (FAT) domain / Focal adhesion kinase, targeting (FAT) domain superfamily / Focal adhesion kinase, N-terminal / FAK1/PYK2, FERM domain C-lobe / Focal adhesion targeting region / FERM N-terminal domain / : / FAK1/PYK2, FERM domain C-lobe / FERM domain signature 2. / FERM central domain / FERM/acyl-CoA-binding protein superfamily / FERM central domain / FERM superfamily, second domain / FERM domain / FERM domain profile. / Band 4.1 domain / Band 4.1 homologues / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / PH-like domain superfamily / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Ubiquitin-like domain superfamily / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
Focal adhesion kinase 1
Similarity search - Component
Biological speciesGallus gallus (chicken)
Methodsingle particle reconstruction / cryo EM / Resolution: 6.32 Å
AuthorsAcebron I / Righetto R
Funding support Spain, Switzerland, 2 items
OrganizationGrant numberCountry
Spanish Ministry of Science, Innovation, and Universities Spain
Swiss National Science Foundation Switzerland
CitationJournal: EMBO J / Year: 2020
Title: Structural basis of Focal Adhesion Kinase activation on lipid membranes.
Authors: Iván Acebrón / Ricardo D Righetto / Christina Schoenherr / Svenja de Buhr / Pilar Redondo / Jayne Culley / Carlos F Rodríguez / Csaba Daday / Nikhil Biyani / Oscar Llorca / Adam Byron / ...Authors: Iván Acebrón / Ricardo D Righetto / Christina Schoenherr / Svenja de Buhr / Pilar Redondo / Jayne Culley / Carlos F Rodríguez / Csaba Daday / Nikhil Biyani / Oscar Llorca / Adam Byron / Mohamed Chami / Frauke Gräter / Jasminka Boskovic / Margaret C Frame / Henning Stahlberg / Daniel Lietha /
Abstract: Focal adhesion kinase (FAK) is a key component of the membrane proximal signaling layer in focal adhesion complexes, regulating important cellular processes, including cell migration, proliferation, ...Focal adhesion kinase (FAK) is a key component of the membrane proximal signaling layer in focal adhesion complexes, regulating important cellular processes, including cell migration, proliferation, and survival. In the cytosol, FAK adopts an autoinhibited state but is activated upon recruitment into focal adhesions, yet how this occurs or what induces structural changes is unknown. Here, we employ cryo-electron microscopy to reveal how FAK associates with lipid membranes and how membrane interactions unlock FAK autoinhibition to promote activation. Intriguingly, initial binding of FAK to the membrane causes steric clashes that release the kinase domain from autoinhibition, allowing it to undergo a large conformational change and interact itself with the membrane in an orientation that places the active site toward the membrane. In this conformation, the autophosphorylation site is exposed and multiple interfaces align to promote FAK oligomerization on the membrane. We show that interfaces responsible for initial dimerization and membrane attachment are essential for FAK autophosphorylation and resulting cellular activity including cancer cell invasion, while stable FAK oligomerization appears to be needed for optimal cancer cell proliferation in an anchorage-independent manner. Together, our data provide structural details of a key membrane bound state of FAK that is primed for efficient autophosphorylation and activation, hence revealing the critical event in integrin mediated FAK activation and signaling at focal adhesions.
History
DepositionJan 15, 2020-
Header (metadata) releaseAug 19, 2020-
Map releaseAug 19, 2020-
UpdateMay 22, 2024-
Current statusMay 22, 2024Processing site: PDBe / Status: Released

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Structure visualization

Movie
  • Surface view with section colored by density value
  • Surface level: 0.03
  • Imaged by UCSF Chimera
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  • Surface view colored by height
  • Surface level: 0.03
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  • Surface view with fitted model
  • Atomic models: PDB-6ty3
  • Surface level: 0.03
  • Imaged by UCSF Chimera
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  • Simplified surface model + fitted atomic model
  • Atomic modelsPDB-6ty3
  • Imaged by Jmol
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Movie viewer
Structure viewerEM map:
SurfViewMolmilJmol/JSmol
Supplemental images

emd_10615.png

Downloads & links

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Map

FileDownload / File: emd_10615.map.gz / Format: CCP4 / Size: 51.4 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationMap obtained from single particle analysis of FAK 2D crystals.
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.7 Å/pix.
x 238 pix.
= 404.6 Å		1.7 Å/pix.
x 238 pix.
= 404.6 Å		1.7 Å/pix.
x 238 pix.
= 404.6 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.7 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.03 / Movie #1: 0.03
Minimum - Maximum-0.084483296 - 0.13689257
Average (Standard dev.)-0.0001933634 (±0.008126085)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions238238238
Spacing238238238
CellA=B=C: 404.6 Å
α=β=γ: 90.0 °

CCP4 map header:

modeImage stored as Reals
Å/pix. X/Y/Z1.71.71.7
M x/y/z238238238
origin x/y/z0.0000.0000.000
length x/y/z404.600404.600404.600
α/β/γ90.00090.00090.000
start NX/NY/NZ000
NX/NY/NZ280280280
MAP C/R/S123
start NC/NR/NS000
NC/NR/NS238238238
D min/max/mean-0.0840.137-0.000

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Supplemental data

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Mask #1

Fileemd_10615_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_10615_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_10615_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Focal adhesion kinase

EntireName: Focal adhesion kinase
Components
  • Complex: Focal adhesion kinase
    • Protein or peptide: Focal adhesion kinase 1

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Supramolecule #1: Focal adhesion kinase

SupramoleculeName: Focal adhesion kinase / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Gallus gallus (chicken)
Molecular weightTheoretical: 150 KDa

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Macromolecule #1: Focal adhesion kinase 1

MacromoleculeName: Focal adhesion kinase 1 / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: non-specific protein-tyrosine kinase
Source (natural)Organism: Gallus gallus (chicken)
Molecular weightTheoretical: 75.476445 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GPGAMERVLK VFHYFENSSE PTTWASIIRH GDATDVRGII QKIVDCHKVK NVACYGLRLS HLQSEEVHWL HLDMGVSNVR EKFELAHPP EEWKYELRIR YLPKGFLNQF TEDKPTLNFF YQQVKNDYML EIADQVDQEI ALKLGCLEIR RSYGEMRGNA L EKKSNYEV ...String:
GPGAMERVLK VFHYFENSSE PTTWASIIRH GDATDVRGII QKIVDCHKVK NVACYGLRLS HLQSEEVHWL HLDMGVSNVR EKFELAHPP EEWKYELRIR YLPKGFLNQF TEDKPTLNFF YQQVKNDYML EIADQVDQEI ALKLGCLEIR RSYGEMRGNA L EKKSNYEV LEKDVGLRRF FPKSLLDSVK AKTLRKLIQQ TFRQFANLNR EESILKFFEI LSPVYRFDKE CFKCALGSSW II SVELAIG PEEGISYLTD KGANPTHLAD FNQVQTIQYS NSEDKDRKGM LQLKIAGAPE PLTVTAPSLT IAENMADLID GYC RLVNGA TQSFIIRPQK EGERALPSIP KLANNEKQGV RSHTVSVSET DDYAEIIDEE DTYTMPSTRD YEIQRERIEL GRCI GEGQF GDVHQGIYMS PENPAMAVAI KTCKNCTSDS VREKFLQEAL TMRQFDHPHI VKLIGVITEN PVWIIMELCT LGELR SFLQ VRKFSLDLAS LILYAYQLST ALAYLESKRF VHRDIAARNV LVSATDCVKL GDFGLSRYME DSTYYKASKG KLPIKW MAP ESINFRRFTS ASDVWMFGVC MWEILMHGVK PFQGVKNNDV IGRIENGERL PMPPNCPPTL YSLMTKCWAY DPSRRPR FT ELKAQLSTIL EEEKLQ

UniProtKB: Focal adhesion kinase 1

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation state2D array

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Sample preparation

BufferpH: 5.5
VitrificationCryogen name: ETHANE

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Electron microscopy #1

Microscopy ID1
MicroscopeFEI TITAN KRIOS
Image recordingImage recording ID: 1 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsC2 aperture diameter: 100.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Electron microscopy #1~

Microscopy ID1
MicroscopeFEI POLARA 300
Image recordingImage recording ID: 2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.26 mm
Experimental equipment
Model: Tecnai Polara / Image courtesy: FEI Company

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Image processing

Image recording ID1
Startup modelType of model: INSILICO MODEL
Final reconstructionApplied symmetry - Point group: C2 (2 fold cyclic) / Algorithm: FOURIER SPACE / Resolution.type: BY AUTHOR / Resolution: 6.32 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 106785
Initial angle assignmentType: OTHER
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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Atomic model buiding 1

Initial model
PDB IDChain

2aeh

chain_id: A, residue_range: 33-363, source_name: PDB, initial_model_type: experimental model

1mp8

chain_id: A, residue_range: 414-686, source_name: PDB, initial_model_type: experimental model
RefinementSpace: REAL / Protocol: FLEXIBLE FIT
Output model

PDB-6ty3:
FAK structure from single particle analysis of 2D crystals

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