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- PDB-22ve: Cryo-EM structure of DOCK11 complexed with Cdc42(G15A) -

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Basic information

Entry
Database: PDB / ID: 22ve
TitleCryo-EM structure of DOCK11 complexed with Cdc42(G15A)
Components
  • Cell division control protein 42 homolog
  • Dedicator of cytokinesis protein 11
KeywordsSIGNALING PROTEIN / RhoGEF / complex
Function / homology
Function and homology information


marginal zone B cell differentiation / 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 / B cell homeostasis ...marginal zone B cell differentiation / 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 / B cell homeostasis / 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 / regulation of postsynapse organization / positive regulation of filopodium assembly / CD28 dependent Vav1 pathway / Wnt signaling pathway, planar cell polarity pathway / phagocytosis, engulfment / RHOV GTPase cycle / Myogenesis / establishment of cell polarity / spindle midzone / small GTPase-mediated signal transduction / 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 GTPase activity / positive regulation of stress fiber assembly / RHO GTPases Activate WASPs and WAVEs / positive regulation of lamellipodium assembly / positive regulation of substrate adhesion-dependent cell spreading / 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 / actin filament organization / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / guanyl-nucleotide exchange factor activity / integrin-mediated signaling pathway / acrosomal vesicle / regulation of actin cytoskeleton organization / endocytosis / FCGR3A-mediated phagocytosis / small monomeric GTPase / filopodium / SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST) / EGFR downregulation / RHO GTPases Activate Formins / Regulation of actin dynamics for phagocytic cup formation / VEGFA-VEGFR2 Pathway / mitotic spindle / MAPK6/MAPK4 signaling / small GTPase binding / apical part of cell / cytoplasmic ribonucleoprotein granule / microtubule cytoskeleton / actin cytoskeleton organization / Activation of STAT3 by cadherin engagement / 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
Similarity search - Function
Dedicator of cytokinesis D, C2 domain / Dedicator of cytokinesis C/D, N-terminal / : / Dedicator of cytokinesis C/D, N terminal / DOCK6-11, TPR domain / Cdc42 / Dedicator of cytokinesis / C2 DOCK-type domain / DOCKER domain / Dedicator of cytokinesis, C-terminal, lobe A ...Dedicator of cytokinesis D, C2 domain / Dedicator of cytokinesis C/D, N-terminal / : / Dedicator of cytokinesis C/D, N terminal / DOCK6-11, TPR domain / Cdc42 / 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. / PH domain / PH domain profile. / C2 domain superfamily / Pleckstrin homology domain. / Pleckstrin homology domain / 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 / PH-like domain superfamily / Armadillo-type fold / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Cell division control protein 42 homolog / Dedicator of cytokinesis protein 11
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.28 Å
AuthorsHisano, T. / Kukimoto-Niino, M. / Shinoda, T. / Katsura, K. / Shirouzu, M.
Funding support Japan, 3items
OrganizationGrant numberCountry
Japan Science and TechnologyJPMJCR22E3 Japan
Other governmentNational Center for Geriatrics and Gerontology, 24-7
Other privateBiology of Intracellular Environments
CitationJournal: Proc Natl Acad Sci U S A / Year: 2026
Title: Structural basis for membrane-dependent positive feedback regulation of DOCK11 by activated Cdc42.
Authors: Tamao Hisano / Takehiro Shinoda / Mutsuko Kukimoto-Niino / Kazushige Katsura / Ryohei Kondo / Yoshiko Ishizuka-Katsura / Yukako Miyata-Yabuki / Kazuharu Hanada / Reiko Nakagawa / Akihiko ...Authors: Tamao Hisano / Takehiro Shinoda / Mutsuko Kukimoto-Niino / Kazushige Katsura / Ryohei Kondo / Yoshiko Ishizuka-Katsura / Yukako Miyata-Yabuki / Kazuharu Hanada / Reiko Nakagawa / Akihiko Nishikimi / Mikako Shirouzu /
Abstract: The guanine nucleotide exchange factor DOCK11 is widely expressed across tissues and activates Cdc42, a Rho family GTPase that regulates cytoskeletal remodeling and cell polarity. Loss-of-function ...The guanine nucleotide exchange factor DOCK11 is widely expressed across tissues and activates Cdc42, a Rho family GTPase that regulates cytoskeletal remodeling and cell polarity. Loss-of-function mutations in DOCK11 have recently been linked to inborn errors of immunity. DOCK11 has also been implicated in facilitating hepatitis B virus infection in hepatocytes and has emerged as a potential target for therapeutic interventions. A positive feedback mechanism has been proposed for DOCK11-mediated Cdc42 activation; however, the structural basis for this regulation has remained unclear. Here we report the cryoelectron microscopy structures of full-length DOCK11 as an apo dimer, a binary complex with nucleotide-free Cdc42, and a ternary complex containing both nucleotide-free and activated Cdc42. DOCK11 predominantly adopts a U-shaped dimer that binds to nucleotide-free Cdc42 via the catalytic domain, whereas activated Cdc42 engages a distal site within the armadillo-repeat domain. Biochemical and cellular analyses demonstrate that binding of activated Cdc42 is critical for enhancing the membrane-dependent nucleotide exchange activity of DOCK11, promoting its localization to the plasma membrane, and facilitating intracellular activation of Cdc42. We also determined the structure of the membrane-bound ternary complex using membrane-coated grids. Strikingly, the ternary complex adopts an extended conformation that aligns multiple membrane-contact elements, revealing how activated Cdc42 stabilizes DOCK11 membrane binding for efficient exchange activity. Collectively, these findings provide a structural framework for the coordinated mechanism underlying membrane-dependent positive feedback in Rho GTPase signaling.
History
DepositionJan 25, 2026Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Oct 21, 2026Provider: repository / Type: Initial release
Revision 1.0Oct 21, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Dedicator of cytokinesis protein 11
B: Dedicator of cytokinesis protein 11
C: Cell division control protein 42 homolog
D: Cell division control protein 42 homolog


Theoretical massNumber of molelcules
Total (without water)519,7434
Polymers519,7434
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein Dedicator of cytokinesis protein 11 / Activated Cdc42-associated guanine nucleotide exchange factor / ACG / Zizimin-2


Mass: 238396.047 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DOCK11, ZIZ2 / Cell line (production host): FreeStyle 293-F / Production host: Homo sapiens (human) / References: UniProt: Q5JSL3
#2: Protein Cell division control protein 42 homolog / G25K GTP-binding 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) / Description: cell-free synthesis / Gene: CDC42 / Production host: Escherichia coli (E. coli) / References: UniProt: P60953, small monomeric GTPase
Has protein modificationN

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Binary complex of DOCK11 with Cdc42(G15A) / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Molecular weightExperimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Homo sapiens (human)
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm
Specimen holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingElectron dose: 50.4 e/Å2 / Film or detector model: GATAN K3 BIOCONTINUUM (6k x 4k)

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Processing

EM software
IDNameVersionCategory
1cryoSPARCparticle selection
4cryoSPARCCTF correction
9cryoSPARCinitial Euler assignment
10cryoSPARCfinal Euler assignment
11cryoSPARCclassification
12cryoSPARC3D reconstruction
13PHENIX1.21_5207model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C2 (2 fold cyclic)
3D reconstructionResolution: 4.28 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 117660 / Symmetry type: POINT
Atomic model buildingProtocol: RIGID BODY FIT / Space: REAL
Atomic model building

3D fitting-ID: 1 / Source name: PDB / Type: experimental model

IDPDB-IDPdb chain-IDAccession codeChain-IDDetails (eV)Initial refinement model-IDChain residue rangePdb chain residue range
122VF

22vf

A22VFADOCK111
22WM9

2wm9

B2WM9BCdc42(G15A)21-1771-177
RefinementHighest resolution: 4.28 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00431678
ELECTRON MICROSCOPYf_angle_d0.66242850
ELECTRON MICROSCOPYf_dihedral_angle_d4.7564148
ELECTRON MICROSCOPYf_chiral_restr0.0414812
ELECTRON MICROSCOPYf_plane_restr0.0055470

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