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- EMDB-65179: Structure of DOCK6 tetramer complexed with Rac1 -

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Basic information

Entry
Database: EMDB / ID: EMD-65179
TitleStructure of DOCK6 tetramer complexed with Rac1
Map data
Sample
  • Complex: DOCK6 tetramer complexed with Rac1
    • Protein or peptide: Dedicator of cytokinesis protein 6
    • Protein or peptide: Ras-related C3 botulinum toxin substrate 1
KeywordsDOCK / GEF / Rho / small GTPase / Rac / Cdc42 / SIGNALING PROTEIN
Function / homology
Function and homology information


regulation of respiratory burst / positive regulation of ovarian follicle development / regulation of neutrophil migration / negative regulation of interleukin-23 production / Activated NTRK2 signals through CDK5 / negative regulation of fibroblast migration / ruffle assembly / localization within membrane / kinocilium / regulation of cell adhesion involved in heart morphogenesis ...regulation of respiratory burst / positive regulation of ovarian follicle development / regulation of neutrophil migration / negative regulation of interleukin-23 production / Activated NTRK2 signals through CDK5 / negative regulation of fibroblast migration / ruffle assembly / localization within membrane / kinocilium / regulation of cell adhesion involved in heart morphogenesis / NTRK2 activates RAC1 / NADPH oxidase complex / Inactivation of CDC42 and RAC1 / regulation of hydrogen peroxide metabolic process / Rac protein signal transduction / engulfment of apoptotic cell / superoxide anion generation / WNT5:FZD7-mediated leishmania damping / SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion / respiratory burst / motor neuron axon guidance / ruffle organization / positive regulation of bicellular tight junction assembly / GTP-dependent protein binding / regulation of Rho protein signal transduction / midbrain dopaminergic neuron differentiation / regulation of lamellipodium assembly / thioesterase binding / regulation of stress fiber assembly / RHO GTPases activate CIT / regulation of nitric oxide biosynthetic process / Nef and signal transduction / Activation of RAC1 / PCP/CE pathway / hepatocyte growth factor receptor signaling pathway / RHO GTPases activate KTN1 / forebrain development / sphingosine-1-phosphate receptor signaling pathway / DCC mediated attractive signaling / MET activates RAP1 and RAC1 / Sema4D mediated inhibition of cell attachment and migration / Azathioprine ADME / lamellipodium assembly / CD28 dependent Vav1 pathway / Ephrin signaling / positive regulation of neutrophil chemotaxis / Wnt signaling pathway, planar cell polarity pathway / positive regulation of ruffle assembly / regulation of receptor signaling pathway via JAK-STAT / NRAGE signals death through JNK / Rho GDP-dissociation inhibitor binding / small GTPase-mediated signal transduction / Activation of RAC1 downstream of NMDARs / positive regulation of Rho protein signal transduction / pericentriolar material / establishment or maintenance of cell polarity / CDC42 GTPase cycle / semaphorin-plexin signaling pathway / RHO GTPases activate PAKs / Sema3A PAK dependent Axon repulsion / EPH-ephrin mediated repulsion of cells / regulation of postsynapse assembly / ficolin-1-rich granule membrane / positive regulation of focal adhesion assembly / RHO GTPases Activate NADPH Oxidases / positive regulation of substrate adhesion-dependent cell spreading / anatomical structure morphogenesis / positive regulation of stress fiber assembly / RHO GTPases Activate WASPs and WAVEs / regulation of synaptic vesicle endocytosis / substrate adhesion-dependent cell spreading / positive regulation of lamellipodium assembly / cell-matrix adhesion / RHO GTPases activate IQGAPs / GPVI-mediated activation cascade / RHO GTPases activate PKNs / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / phagocytic cup / actin filament polymerization / RAC1 GTPase cycle / EPHB-mediated forward signaling / regulation of cell migration / positive regulation of endothelial cell migration / guanyl-nucleotide exchange factor activity / actin filament organization / cell motility / secretory granule membrane / Signal transduction by L1 / positive regulation of insulin secretion involved in cellular response to glucose stimulus / VEGFR2 mediated vascular permeability / small monomeric GTPase / FCGR3A-mediated phagocytosis / cell chemotaxis / FCERI mediated MAPK activation / Translocation of SLC2A4 (GLUT4) to the plasma membrane / response to wounding / trans-Golgi network / SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST) / neuron migration / regulation of cell shape
Similarity search - Function
: / Dedicator of cytokinesis C, C2 domain / Dedicator of cytokinesis C/D, N-terminal / Dedicator of cytokinesis C/D, N terminal / DOCK6-11, TPR domain / Dedicator of cytokinesis / C2 DOCK-type domain / DOCKER domain / Dedicator of cytokinesis, C-terminal, lobe A / Dedicator of cytokinesis, C-terminal, lobe C ...: / Dedicator of cytokinesis C, C2 domain / Dedicator of cytokinesis C/D, N-terminal / Dedicator of cytokinesis C/D, N terminal / DOCK6-11, TPR domain / Dedicator of cytokinesis / C2 DOCK-type domain / DOCKER domain / Dedicator of cytokinesis, C-terminal, lobe A / Dedicator of cytokinesis, C-terminal, lobe C / DOCKER, Lobe A / DOCKER, Lobe B / DOCKER, Lobe C / DHR-2, Lobe A / C2 domain in Dock180 and Zizimin proteins / DHR-2, Lobe C / DHR-2, Lobe B / C2 DOCK-type domain profile. / DOCKER domain profile. / Small GTPase Rho / Small GTPase Rho domain profile. / C2 domain superfamily / Rho (Ras homology) subfamily of Ras-like small GTPases / Ras subfamily of RAS small GTPases / Small GTPase / Ras family / Rab subfamily of small GTPases / Small GTP-binding protein domain / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Ras-related C3 botulinum toxin substrate 1 / Dedicator of cytokinesis protein 6
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 6.85 Å
AuthorsKukimoto-Niino M / Katsura K / Ishizuka-Katsura Y / Yonemochi M / Hanada K / Shirouzu M
Funding support Japan, 4 items
OrganizationGrant numberCountry
Japan Society for the Promotion of Science (JSPS)JP15K06987 Japan
Japan Society for the Promotion of Science (JSPS)JP22H05551 Japan
Japan Society for the Promotion of Science (JSPS)JP25K02219 Japan
Japan Science and TechnologyJPMJCR22E3 Japan
CitationJournal: Commun Biol / Year: 2026
Title: 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
DepositionJun 27, 2025-
Header (metadata) releaseJun 3, 2026-
Map releaseJun 3, 2026-
UpdateSep 9, 2026-
Current statusSep 9, 2026Processing site: PDBj / Status: Released

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Structure visualization

Supplemental images

emd_65179.png

Downloads & links

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Map

FileDownload / File: emd_65179.map.gz / Format: CCP4 / Size: 149.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

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AxesZ (Sec.)Y (Row.)X (Col.)
1.33 Å/pix.
x 340 pix.
= 452.2 Å		1.33 Å/pix.
x 340 pix.
= 452.2 Å		1.33 Å/pix.
x 340 pix.
= 452.2 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.33 Å
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Histogram (log scale)
Contour LevelBy AUTHOR: 0.01
Minimum - Maximum-0.0576953 - 0.0948634
Average (Standard dev.)0.000023845949 (±0.0030509369)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions340340340
Spacing340340340
CellA=B=C: 452.2 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: half2 map

Fileemd_65179_half_map_1.map
Annotationhalf2 map
Projections & Slices
AxesZYX

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Slices (1/2)
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Half map: half1 map

Fileemd_65179_half_map_2.map
Annotationhalf1 map
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Histogram

Histogram (log scale)

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Sample components

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Entire : DOCK6 tetramer complexed with Rac1

EntireName: DOCK6 tetramer complexed with Rac1
Components
  • Complex: DOCK6 tetramer complexed with Rac1
    • Protein or peptide: Dedicator of cytokinesis protein 6
    • Protein or peptide: Ras-related C3 botulinum toxin substrate 1

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Supramolecule #1: DOCK6 tetramer complexed with Rac1

SupramoleculeName: DOCK6 tetramer complexed with Rac1 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Dedicator of cytokinesis protein 6

MacromoleculeName: Dedicator of cytokinesis protein 6 / type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 230.265312 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: GGSGGSMAAS ERRAFAHKIN RTVAAEVRKQ VSRERSGSPH SSRRCSSSLG VPLTEVVEPL DFEDVLLSRP PDAEPGPLRD LVEFPADDL ELLLQPRECR TTEPGIPKDE KLDAQVRAAV EMYIEDWVIV HRRYQYLSAA YSPVTTDTQR ERQKGLPRQV F EQDASGDE ...String:
GGSGGSMAAS ERRAFAHKIN RTVAAEVRKQ VSRERSGSPH SSRRCSSSLG VPLTEVVEPL DFEDVLLSRP PDAEPGPLRD LVEFPADDL ELLLQPRECR TTEPGIPKDE KLDAQVRAAV EMYIEDWVIV HRRYQYLSAA YSPVTTDTQR ERQKGLPRQV F EQDASGDE RSGPEDSNDS RRGSGSPEDT PRSSGASSIF DLRNLAADSL LPSLLERAAP EDVDRRNETL RRQHRPPALL TL YPAPDED EAVERCSRPE PPREHFGQRI LVKCLSLKFE IEIEPIFGIL ALYDVREKKK ISENFYFDLN SDSMKGLLRA HGT HPAIST LARSAIFSVT YPSPDIFLVI KLEKVLQQGD ISECCEPYMV LKEVDTAKNK EKLEKLRLAA EQFCTRLGRY RMPF AWTAV HLANIVSSAG QLDRDSDSEG ERRPAWTDRR RRGPQDRASS GDDACSFSGF RPATLTVTNF FKQEAERLSD EDLFK FLAD MRRPSSLLRR LRPVTAQLKI DISPAPENPH FCLSPELLHI KPYPDPRGRP TKEILEFPAR EVYAPHTSYR NLLYVY PHS LNFSSRQGSV RNLAVRVQYM TGEDPSQALP VIFGKSSCSE FTREAFTPVV YHNKSPEFYE EFKLHLPACV TENHHLL FT FYHVSCQPRP GTALETPVGF TWIPLLQHGR LRTGPFCLPV SVDQPPPSYS VLTPDVALPG MRWVDGHKGV FSVELTAV S SVHPQDPYLD KFFTLVHVLE EGAFPFRLKD TVLSEGNVEQ ELRASLAALR LASPEPLVAF SHHVLDKLVR LVIRPPIIS GQIVNLGRGA FEAMAHVVSL VHRSLEAAQD ARGHCPQLAA YVHYAFRLPG TEPSLPDGAP PVTVQAATLA RGSGRPASLY LARSKSISS SNPDLAVAPG SVDDEVSRIL ASKLLHEELA LQWVVSSSAV REAILQHAWF FFQLMVKSMA LHLLLGQRLD T PRKLRFPG RFLDDITALV GSVGLEVITR VHKDVELAEH LNASLAFFLS DLLSLVDRGF VFSLVRAHYK QVATRLQSSP NP AALLTLR MEFTRILCSH EHYVTLNLPC CPLSPPASPS PSVSSTTSQS STFSSQAPDP KVTSMFELSG PFRQQHFLAG LLL TELALA LEPEAEGAFL LHKKAISAVH SLLCGHDTDP RYAEATVKAR VAELYLPLLS IARDTLPRLH DFAEGPGQRS RLAS MLDSD TEGEGDIAGT INPSVAMAIA GGPLAPGSRA SISQGPPTAS RAGCALSAES SRTLLACVLW VLKNTEPALL QRWAT DLTL PQLGRLLDLL YLCLAAFEYK GKKAFERINS LTFKKSLDMK ARLEEAILGT IGARQEMVRR SRERSPFGNP ENVRWR KSV THWKQTSDRV DKTKDEMEHE ALVEGNLATE ASLVVLDTLE IIVQTVMLSE ARESVLGAVL KVVLYSLGSA QSALFLQ HG LATQRALVSK FPELLFEEDT ELCADLCLRL LRHCGSRIST IRTHASASLY LLMRQNFEIG HNFARVKMQV TMSLSSLV G TTQNFSEEHL RRSLKTILTY AEEDMGLRDS TFAEQVQDLM FNLHMILTDT VKMKEHQEDP EMLIDLMYRI ARGYQGSPD LRLTWLQNMA GKHAELGNHA EAAQCMVHAA ALVAEYLALL EDHRHLPVGC VSFQNISSNV LEESAISDDI LSPDEEGFCS GKHFTELGL VGLLEQAAGY FTMGGLYEAV NEVYKNLIPI LEAHRDYKKL AAVHGKLQEA FTKIMHQSSG WERVFGTYFR V GFYGAHFG DLDEQEFVYK EPSITKLAEI SHRLEEFYTE RFGDDVVEII KDSNPVDKSK LDSQKAYIQI TYVEPYFDTY EL KDRVTYF DRNYGLRTFL FCTPFTPDGR AHGELPEQHK RKTLLSTDHA FPYIKTRIRV CHREETVLTP VEVAIEDMQK KTR ELAFAT EQDPPDAKML QMVLQGSVGP TVNQGPLEVA QVFLAEIPED PKLFRHHNKL RLCFKDFCKK CEDALRKNKA LIGP DQKEY HRELERNYCR LREALQPLLT QRLPQLMAPT PPGLRNSLNR ASFRKADL

UniProtKB: Dedicator of cytokinesis protein 6

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Macromolecule #2: Ras-related C3 botulinum toxin substrate 1

MacromoleculeName: Ras-related C3 botulinum toxin substrate 1 / type: protein_or_peptide / ID: 2 / Number of copies: 4 / Enantiomer: LEVO / EC number: small monomeric GTPase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 20.244258 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString:
GSSGSSGMQA IKCVVVGDGA VAKTCLLISY TTNAFPGEYI PTVFDNYSAN VMVDGKPVNL GLWDTAGQED YDRLRPLSYP QTDVFLICF SLVSPASFEN VRAKWYPEVR HHCPNTPIIL VGTKLDLRDD KDTIEKLKEK KLTPITYPQG LAMAKEIGAV K YLECSALT QRGLKTVFDE AIRAVL

UniProtKB: Ras-related C3 botulinum toxin substrate 1

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 8
GridModel: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: CONTINUOUS
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Number real images: 5048 / Average electron dose: 49.5 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 64000
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Particle selectionNumber selected: 21977481
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionApplied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 6.85 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION (ver. 3.1) / Number images used: 112745
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
Final 3D classificationNumber classes: 5 / Software - Name: RELION (ver. 3.1)
FSC plot (resolution estimation)

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