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Open data
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Basic information
| Entry | Database: PDB / ID: 9vm3 | ||||||||||||||||||||||||
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| Title | Structure of DOCK6-Cdc42 complex | ||||||||||||||||||||||||
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Keywords | SIGNALING PROTEIN / DOCK / GEF / Rho / small GTPase / Rac / Cdc42 | ||||||||||||||||||||||||
| Function / homology | Function and homology informationGBD domain binding / positive regulation of pinocytosis / COG complex / cardiac neural crest cell migration involved in outflow tract morphogenesis / storage vacuole / positive regulation of epithelial cell proliferation involved in lung morphogenesis / apolipoprotein A-I receptor binding / regulation of attachment of spindle microtubules to kinetochore / embryonic heart tube development / organelle transport along microtubule ...GBD domain binding / positive regulation of pinocytosis / COG complex / cardiac neural crest cell migration involved in outflow tract morphogenesis / storage vacuole / positive regulation of epithelial cell proliferation involved in lung morphogenesis / apolipoprotein A-I receptor binding / regulation of attachment of spindle microtubules to kinetochore / embryonic heart tube development / organelle transport along microtubule / endothelin receptor signaling pathway / Inactivation of CDC42 and RAC1 / positive regulation of pseudopodium assembly / host-mediated perturbation of viral process / leading edge membrane / regulation of filopodium assembly / neuropilin signaling pathway / establishment of Golgi localization / dendritic spine morphogenesis / establishment of epithelial cell apical/basal polarity / cell junction assembly / GTP-dependent protein binding / regulation of Rho protein signal transduction / heart process / regulation of lamellipodium assembly / thioesterase binding / regulation of stress fiber assembly / RHO GTPases activate KTN1 / DCC mediated attractive signaling / positive regulation of filopodium assembly / CD28 dependent Vav1 pathway / regulation of postsynapse organization / Wnt signaling pathway, planar cell polarity pathway / phagocytosis, engulfment / RHOV GTPase cycle / Myogenesis / establishment of cell polarity / small GTPase-mediated signal transduction / spindle midzone / positive regulation of cytokinesis / RHOJ GTPase cycle / RHOQ GTPase cycle / Golgi organization / RHOU GTPase cycle / macrophage differentiation / establishment or maintenance of cell polarity / CDC42 GTPase cycle / RHO GTPases activate PAKs / RHOG GTPase cycle / RAC3 GTPase cycle / RAC2 GTPase cycle / positive regulation of substrate adhesion-dependent cell spreading / positive regulation of stress fiber assembly / RHO GTPases Activate WASPs and WAVEs / positive regulation of lamellipodium assembly / negative regulation of protein-containing complex assembly / RHO GTPases activate IQGAPs / GPVI-mediated activation cascade / RAC1 GTPase cycle / phagocytic vesicle / EPHB-mediated forward signaling / substantia nigra development / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / guanyl-nucleotide exchange factor activity / actin filament organization / integrin-mediated signaling pathway / acrosomal vesicle / regulation of actin cytoskeleton organization / small monomeric GTPase / FCGR3A-mediated phagocytosis / filopodium / SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST) / endocytosis / EGFR downregulation / RHO GTPases Activate Formins / Regulation of actin dynamics for phagocytic cup formation / VEGFA-VEGFR2 Pathway / mitotic spindle / MAPK6/MAPK4 signaling / Activation of STAT3 by cadherin engagement / apical part of cell / cytoplasmic ribonucleoprotein granule / microtubule cytoskeleton / actin cytoskeleton organization / cell-cell junction / G beta:gamma signalling through CDC42 / ubiquitin protein ligase activity / positive regulation of cell growth / Factors involved in megakaryocyte development and platelet production / midbody / G protein activity / neuron projection / postsynapse / positive regulation of cell migration / Golgi membrane / focal adhesion / centrosome / neuronal cell body / GTPase activity / dendrite Similarity search - Function | ||||||||||||||||||||||||
| Biological species | Homo sapiens (human) | ||||||||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.52 Å | ||||||||||||||||||||||||
Authors | Kukimoto-Niino, M. / Katsura, K. / Ishizuka-Katsura, Y. / Yonemochi, M. / Hanada, K. / Shirouzu, M. | ||||||||||||||||||||||||
| Funding support | Japan, 4items
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Citation | Journal: Commun Biol / Year: 2026Title: Structural basis for auto-inhibition of the Rac1/Cdc42 guanine nucleotide exchange factor DOCK6 by oligomer formation. Authors: Mutsuko Kukimoto-Niino / Kazushige Katsura / Kota Yoshimura / Yoshiko Ishizuka-Katsura / Yuki Miyamoto / Mayumi Yonemochi / Kazuharu Hanada / Junji Yamauchi / Richard W Wong / Mikako Shirouzu / ![]() Abstract: The guanine nucleotide exchange factor DOCK6 is important for neurite outgrowth, as well as cell migration and invasion, through the activation of Rac1 and Cdc42-members of the Rho family of GTPases ...The guanine nucleotide exchange factor DOCK6 is important for neurite outgrowth, as well as cell migration and invasion, through the activation of Rac1 and Cdc42-members of the Rho family of GTPases that regulate the actin cytoskeleton. However, the precise molecular mechanisms by which DOCK6 regulates the intracellular GTPase signaling remain unclear. Here, we present cryo-electron microscopy structures of DOCK6 alone and in complex with Rac1 and Cdc42. The DOCK6-Rac1 and DOCK6-Cdc42 complexes exhibit similar homodimeric structures, with local differences in the catalytic domain of DOCK6 owing to distinct interactions with Rac1 and Cdc42. In contrast, apo-DOCK6 exhibits a closed auto-inhibited conformation in tetrameric and octameric assemblies, with the catalytic and membrane-binding domains contacting each other between two DOCK6 dimers. High-speed atomic force microscopy reveals transitions among multiple oligomers in solution. Biochemical and cellular functional analyses demonstrate that the N-terminal region of DOCK6 plays an auto-inhibitory role, supporting the structural findings. Overall, we propose a mechanism by which DOCK6 activity is spatiotemporally regulated within cells through oligomerization. These findings provide a framework for future studies of DOCK-family GEFs and their broader roles in cell regulation and human disease. | ||||||||||||||||||||||||
| History |
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Structure visualization
| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 9vm3.cif.gz | 669.8 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb9vm3.ent.gz | 536.7 KB | Display | PDB format |
| PDBx/mmJSON format | 9vm3.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/vm/9vm3 ftp://data.pdbj.org/pub/pdb/validation_reports/vm/9vm3 | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 65175MC ![]() 9vm2C ![]() 9vm4C ![]() 9vm5C ![]() 9vm6C ![]() 9vm7C ![]() 9vm8C C: citing same article ( M: map data used to model this data |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
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Assembly
| Deposited unit | ![]()
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Components
| #1: Protein | Mass: 230265.312 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: DOCK6, KIAA1395 / Production host: Homo sapiens (human) / References: UniProt: Q96HP0#2: Protein | Mass: 21475.562 Da / Num. of mol.: 2 / Mutation: G15A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: CDC42 / Production host: ![]() Has protein modification | N | |
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-Experimental details
-Experiment
| Experiment | Method: ELECTRON MICROSCOPY |
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| EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
| Component | Name: Binary complex of DOCK6 with Cdc42 / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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| Source (natural) | Organism: Homo sapiens (human) |
| Source (recombinant) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 8 |
| Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| Specimen support | Grid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
| Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy imaging
| Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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| Microscopy | Model: TFS KRIOS |
| Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 64000 X / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm |
| Image recording | Electron dose: 48.5 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of real images: 3377 |
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Processing
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| CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
| Particle selection | Num. of particles selected: 1936198 | ||||||||||||||||||||||||
| Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
| 3D reconstruction | Resolution: 4.52 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 370326 / Symmetry type: POINT | ||||||||||||||||||||||||
| Refinement | Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS) | ||||||||||||||||||||||||
| Refine LS restraints |
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About Yorodumi




Homo sapiens (human)
Japan, 4items
Citation












PDBj

















FIELD EMISSION GUN