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- EMDB-26734: Cryo-EM structure of WAVE regulatory complex with Rac1 bound on b... -
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Basic information
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Title | Cryo-EM structure of WAVE regulatory complex with Rac1 bound on both A and D site | |||||||||
![]() | WRC230VCA-2Rac1 complex sharpened map | |||||||||
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![]() | actin regulator / GTPase binding protein / cytoskeletal regulator / CELL INVASION | |||||||||
Function / homology | ![]() peripheral region of growth cone / negative regulation of synaptic vesicle recycling / SCAR complex / positive regulation of neurotrophin TRK receptor signaling pathway / lamellipodium morphogenesis / positive regulation of Arp2/3 complex-mediated actin nucleation / Arp2/3 complex binding / modification of synaptic structure / regulation of actin polymerization or depolymerization / central region of growth cone ...peripheral region of growth cone / negative regulation of synaptic vesicle recycling / SCAR complex / positive regulation of neurotrophin TRK receptor signaling pathway / lamellipodium morphogenesis / positive regulation of Arp2/3 complex-mediated actin nucleation / Arp2/3 complex binding / modification of synaptic structure / regulation of actin polymerization or depolymerization / central region of growth cone / modification of postsynaptic actin cytoskeleton / regulation of respiratory burst / dendrite extension / negative regulation of interleukin-23 production / regulation of neutrophil migration / regulation of translation at postsynapse, modulating synaptic transmission / localization within membrane / Activated NTRK2 signals through CDK5 / filopodium tip / negative regulation of receptor-mediated endocytosis / regulation of hydrogen peroxide metabolic process / ruffle assembly / engulfment of apoptotic cell / NTRK2 activates RAC1 / Inactivation of CDC42 and RAC1 / NADPH oxidase complex / respiratory burst / WNT5:FZD7-mediated leishmania damping / regulation of modification of postsynaptic actin cytoskeleton / regulation of actin filament polymerization / SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion / cortical cytoskeleton organization / hepatocyte growth factor receptor signaling pathway / RNA 7-methylguanosine cap binding / ruffle organization / thioesterase binding / cell projection assembly / regulation of stress fiber assembly / negative regulation of fibroblast migration / axon extension / RHO GTPases activate CIT / sphingosine-1-phosphate receptor signaling pathway / Nef and signal transduction / motor neuron axon guidance / PCP/CE pathway / positive regulation of neutrophil chemotaxis / regulation of nitric oxide biosynthetic process / RHO GTPases activate KTN1 / Activation of RAC1 / regulation of lamellipodium assembly / positive regulation of ruffle assembly / positive regulation of dendrite development / Azathioprine ADME / MET activates RAP1 and RAC1 / DCC mediated attractive signaling / positive regulation of cell-substrate adhesion / Wnt signaling pathway, planar cell polarity pathway / Sema4D mediated inhibition of cell attachment and migration / CD28 dependent Vav1 pathway / Ephrin signaling / lamellipodium assembly / regulation of myelination / protein kinase A binding / cortical actin cytoskeleton organization / positive regulation of Rho protein signal transduction / establishment or maintenance of cell polarity / regulation of cell size / Activation of RAC1 downstream of NMDARs / small GTPase-mediated signal transduction / Rho GDP-dissociation inhibitor binding / positive regulation of actin filament polymerization / NRAGE signals death through JNK / Rac protein signal transduction / protein kinase A regulatory subunit binding / filamentous actin / dendritic growth cone / RHO GTPases activate PAKs / positive regulation of focal adhesion assembly / lamellipodium membrane / semaphorin-plexin signaling pathway / Sema3A PAK dependent Axon repulsion / ficolin-1-rich granule membrane / excitatory synapse / RHOG GTPase cycle / RHO GTPases Activate NADPH Oxidases / EPH-ephrin mediated repulsion of cells / RAC2 GTPase cycle / RHO GTPases Activate WASPs and WAVEs / RHO GTPases activate IQGAPs / RAC3 GTPase cycle / anatomical structure morphogenesis / positive regulation of axon extension / axonal growth cone / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / positive regulation of lamellipodium assembly / response to electrical stimulus / positive regulation of substrate adhesion-dependent cell spreading / translation repressor activity / RHO GTPases activate PKNs / positive regulation of stress fiber assembly Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 Å | |||||||||
![]() | Ding B / Yang S / Chen B / Chowdhury S | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structures reveal a key mechanism of WAVE regulatory complex activation by Rac1 GTPase. Authors: Bojian Ding / Sheng Yang / Matthias Schaks / Yijun Liu / Abbigale J Brown / Klemens Rottner / Saikat Chowdhury / Baoyu Chen / ![]() ![]() ![]() Abstract: The Rho-family GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization in many essential processes. Rac1 binds to WRC at two distinct sites-the ...The Rho-family GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization in many essential processes. Rac1 binds to WRC at two distinct sites-the A and D sites. Precisely how Rac1 binds and how the binding triggers WRC activation remain unknown. Here we report WRC structures by itself, and when bound to single or double Rac1 molecules, at ~3 Å resolutions by cryogenic-electron microscopy. The structures reveal that Rac1 binds to the two sites by distinct mechanisms, and binding to the A site, but not the D site, drives WRC activation. Activation involves a series of unique conformational changes leading to the release of sequestered WCA (WH2-central-acidic) polypeptide, which stimulates the Arp2/3 complex to polymerize actin. Together with biochemical and cellular analyses, the structures provide a novel mechanistic understanding of how the Rac1-WRC-Arp2/3-actin signaling axis is regulated in diverse biological processes and diseases. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 13.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 32.6 KB 32.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.7 KB | Display | ![]() |
Images | ![]() | 142 KB | ||
Masks | ![]() | 64 MB | ![]() | |
Filedesc metadata | ![]() | 9.3 KB | ||
Others | ![]() ![]() ![]() | 48.1 MB 46.7 MB 46.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7useMC ![]() 7uscC ![]() 7usdC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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 | WRC230VCA-2Rac1 complex sharpened map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.8757 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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Density Histograms |
-Additional map: WRC230VCA-2Rac1 complex masked unsharpened map
File | emd_26734_additional_1.map | ||||||||||||
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Annotation | WRC230VCA-2Rac1 complex masked unsharpened map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: WRC230VCA-2Rac1 complex unfiltered unmasked unsharpened first half map...
File | emd_26734_half_map_1.map | ||||||||||||
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Annotation | WRC230VCA-2Rac1 complex unfiltered unmasked unsharpened first half map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: WRC230VCA-2Rac1 complex unfiltered unmasked unsharpened second half map...
File | emd_26734_half_map_2.map | ||||||||||||
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Annotation | WRC230VCA-2Rac1 complex unfiltered unmasked unsharpened second half map | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
+Entire : WAVE regulatory complex with Rac1 bound to A and D sites
+Supramolecule #1: WAVE regulatory complex with Rac1 bound to A and D sites
+Macromolecule #1: Cytoplasmic FMR1-interacting protein 1
+Macromolecule #2: Nck-associated protein 1
+Macromolecule #3: Wiskott-Aldrich syndrome protein family member 1
+Macromolecule #4: Protein BRICK1
+Macromolecule #5: Abl interactor 2
+Macromolecule #6: Ras-related C3 botulinum toxin substrate 1
+Macromolecule #7: Ras-related C3 botulinum toxin substrate 1
+Macromolecule #8: PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER
+Macromolecule #9: MAGNESIUM ION
+Macromolecule #10: GUANOSINE-5'-TRIPHOSPHATE
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.15 mg/mL |
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Buffer | pH: 7 |
Grid | Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY ARRAY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 120 sec. / Pretreatment - Atmosphere: AIR / Pretreatment - Pressure: 0.019 kPa / Details: 15 mA |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 95 % / Chamber temperature: 277.15 K / Instrument: HOMEMADE PLUNGER |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Details | Data were collected by shifting the stage to target exposure positions. |
Image recording | Film or detector model: FEI FALCON III (4k x 4k) / Detector mode: COUNTING / Digitization - Dimensions - Width: 4096 pixel / Digitization - Dimensions - Height: 4096 pixel / Number grids imaged: 1 / Number real images: 1285 / Average exposure time: 40.0 sec. / Average electron dose: 41.34 e/Å2 Details: Each micrograph was acquired as dose-fractionated movies consisting of 62 frames per movie. |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.2 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 120000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |