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- EMDB-37593: Vibrio vulnificus MARTX effector duet (RDTND-RID) complexed with ... -
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Basic information
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Title | Vibrio vulnificus MARTX effector duet (RDTND-RID) complexed with human Rac1 Q61L and calmodulin | |||||||||
![]() | pixel size: 0.66extraction box size: 500 pixel (500 x 0.66 = 330 A) | |||||||||
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![]() | MARTX toxin / RDTND-RID / NADase / N-fatty acyl transferase / CaM / Rac1 / TOXIN | |||||||||
Function / homology | ![]() negative regulation of calcium ion transmembrane transporter activity / Ligases; Forming carbon-nitrogen bonds; Acid-amino-acid ligases (peptide synthases) / regulation of respiratory burst / negative regulation of interleukin-23 production / regulation of neutrophil migration / localization within membrane / Activated NTRK2 signals through CDK5 / negative regulation of receptor-mediated endocytosis / regulation of hydrogen peroxide metabolic process / ruffle assembly ...negative regulation of calcium ion transmembrane transporter activity / Ligases; Forming carbon-nitrogen bonds; Acid-amino-acid ligases (peptide synthases) / regulation of respiratory burst / negative regulation of interleukin-23 production / regulation of neutrophil migration / localization within membrane / Activated NTRK2 signals through CDK5 / 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 / SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion / cortical cytoskeleton organization / hepatocyte growth factor receptor signaling pathway / ruffle organization / cell projection assembly / thioesterase binding / regulation of stress fiber assembly / negative regulation of fibroblast migration / 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 / 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 / host cell cytosol / positive regulation of cyclic-nucleotide phosphodiesterase activity / negative regulation of calcium ion export across plasma membrane / positive regulation of Rho protein signal transduction / regulation of cell size / establishment or maintenance of cell polarity / Activation of RAC1 downstream of NMDARs / small GTPase-mediated signal transduction / Rho GDP-dissociation inhibitor binding / acyltransferase activity / NRAGE signals death through JNK / positive regulation of ryanodine-sensitive calcium-release channel activity / Rac protein signal transduction / regulation of cell communication by electrical coupling involved in cardiac conduction / negative regulation of peptidyl-threonine phosphorylation / ligase activity / negative regulation of ryanodine-sensitive calcium-release channel activity / protein phosphatase activator activity / RHO GTPases activate PAKs / positive regulation of focal adhesion assembly / : / semaphorin-plexin signaling pathway / Sema3A PAK dependent Axon repulsion / adenylate cyclase binding / ficolin-1-rich granule membrane / catalytic complex / detection of calcium ion / regulation of cardiac muscle contraction / RHO GTPases Activate NADPH Oxidases / EPH-ephrin mediated repulsion of cells / anatomical structure morphogenesis / RHO GTPases Activate WASPs and WAVEs / RHO GTPases activate IQGAPs / regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion / calcium channel inhibitor activity / PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases / positive regulation of lamellipodium assembly / regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum / positive regulation of substrate adhesion-dependent cell spreading / cysteine-type peptidase activity / : / RHO GTPases activate PKNs / titin binding / regulation of calcium-mediated signaling / positive regulation of protein autophosphorylation / voltage-gated potassium channel complex / Signal transduction by L1 / sperm midpiece / positive regulation of stress fiber assembly / GPVI-mediated activation cascade / positive regulation of microtubule polymerization / calcium channel complex / Transferases; Acyltransferases; Transferring groups other than aminoacyl groups / EPHB-mediated forward signaling / RAC1 GTPase cycle / substantia nigra development / adenylate cyclase activator activity Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 4.32 Å | |||||||||
![]() | Lee Y / Choi S / Jang SY / Hwang J / Kim MH | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Dissemination of pathogenic bacteria is reinforced by a MARTX toxin effector duet. Authors: Sanghyeon Choi / Youngjin Lee / Shinhye Park / Song Yee Jang / Jongbin Park / Do Won Oh / Su-Man Kim / Tae-Hwan Kim / Ga Seul Lee / Changyi Cho / Byoung Sik Kim / Donghan Lee / Eun-Hee Kim / ...Authors: Sanghyeon Choi / Youngjin Lee / Shinhye Park / Song Yee Jang / Jongbin Park / Do Won Oh / Su-Man Kim / Tae-Hwan Kim / Ga Seul Lee / Changyi Cho / Byoung Sik Kim / Donghan Lee / Eun-Hee Kim / Hae-Kap Cheong / Jeong Hee Moon / Ji-Joon Song / Jungwon Hwang / Myung Hee Kim / ![]() Abstract: Multiple bacterial genera take advantage of the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin to invade host cells. Secretion of the MARTX toxin by Vibrio vulnificus, a deadly ...Multiple bacterial genera take advantage of the multifunctional autoprocessing repeats-in-toxin (MARTX) toxin to invade host cells. Secretion of the MARTX toxin by Vibrio vulnificus, a deadly opportunistic pathogen that causes primary septicemia, the precursor of sepsis, is a major driver of infection; however, the molecular mechanism via which the toxin contributes to septicemia remains unclear. Here, we report the crystal and cryo-electron microscopy (EM) structures of a toxin effector duet comprising the domain of unknown function in the first position (DUF1)/Rho inactivation domain (RID) complexed with human targets. These structures reveal how the duet is used by bacteria as a potent weapon. The data show that DUF1 acts as a RID-dependent transforming NADase domain (RDTND) that disrupts NAD homeostasis by hijacking calmodulin. The cryo-EM structure of the RDTND-RID duet complexed with calmodulin and Rac1, together with immunological analyses in vitro and in mice, provide mechanistic insight into how V. vulnificus uses the duet to suppress ROS generation by depleting NAD(P) and modifying Rac1 in a mutually-reinforcing manner that ultimately paralyzes first line immune responses, promotes dissemination of invaders, and induces sepsis. These data may allow development of tools or strategies to combat MARTX toxin-related human diseases. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 448.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 21 KB 21 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 16.5 KB | Display | ![]() |
Images | ![]() | 73 KB | ||
Filedesc metadata | ![]() | 6.3 KB | ||
Others | ![]() ![]() | 442.3 MB 442.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 768.9 KB | Display | ![]() |
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Full document | ![]() | 768.5 KB | Display | |
Data in XML | ![]() | 24.6 KB | Display | |
Data in CIF | ![]() | 32 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8k9zC ![]() 8ka0C ![]() 8ka1C ![]() 8ka2C 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
File | ![]() | ||||||||||||||||||||
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Annotation | pixel size: 0.66extraction box size: 500 pixel (500 x 0.66 = 330 A) | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.66 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: pixel size: 0.66extraction box size: 500 pixel (500 x 0.66 = 330 A)
File | emd_37593_half_map_1.map | ||||||||||||
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Annotation | pixel size: 0.66extraction box size: 500 pixel (500 x 0.66 = 330 A) | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: pixel size: 0.66extraction box size: 500 pixel (500 x 0.66 = 330 A)
File | emd_37593_half_map_2.map | ||||||||||||
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Annotation | pixel size: 0.66extraction box size: 500 pixel (500 x 0.66 = 330 A) | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : RDTND-RID effector duet complexed with Ca2+CaM and Rac1Q61L
Entire | Name: RDTND-RID effector duet complexed with Ca2+CaM and Rac1Q61L |
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Components |
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-Supramolecule #1: RDTND-RID effector duet complexed with Ca2+CaM and Rac1Q61L
Supramolecule | Name: RDTND-RID effector duet complexed with Ca2+CaM and Rac1Q61L type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: RDTND-RID
Supramolecule | Name: RDTND-RID / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 / Details: single mutation, C2838A |
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Source (natural) | Organism: ![]() |
-Supramolecule #3: Calmodulin
Supramolecule | Name: Calmodulin / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 / Details: Sequence conflict, Q124E |
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Source (natural) | Organism: ![]() |
-Supramolecule #4: Rac1
Supramolecule | Name: Rac1 / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #3 / Details: single muatation, Q61L |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: RDTND-RID
Macromolecule | Name: RDTND-RID / type: protein_or_peptide / ID: 1 / Details: single mutant C2838A / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Sequence | String: MGEASHDSAE SLVAARAEKV ANLYRWLDTD NDVATDKYVP VPGFERVDVD VSDEVKQRMI QSMSGYIEHT DNQVPKDQAE ALATLFVEST LDYDWDKRVE FLTKLESYGY SFEAPHAEKS IVSFWSGKNF KQYRDILDNA QTDGKKVVYD IDVKGNAFAI DLNKHLMRWG ...String: MGEASHDSAE SLVAARAEKV ANLYRWLDTD NDVATDKYVP VPGFERVDVD VSDEVKQRMI QSMSGYIEHT DNQVPKDQAE ALATLFVEST LDYDWDKRVE FLTKLESYGY SFEAPHAEKS IVSFWSGKNF KQYRDILDNA QTDGKKVVYD IDVKGNAFAI DLNKHLMRWG GLFLDPDNAE QNQLKSSIDA ATFSNTGFWS SVYATGAQND VYVIAEGGVR LGNYFWNVEL PALRQLQREG LVGEIRLLDK PVSEYKDLPA DQIGRRLTDA GVAVKVRFDA LSHERQAELL ADNPDGYKAD TLVELDVKLS AIDSMLRESL PFYSLRTERN LLVQEGEEGF EVRSWPGIDG KSKTILLDNP EDAAQQKSIE RFILANFDNF EQMPDELFLV DNKVLSHHDG RTRIIAQKED GAWTYNTNVE LMSVTELLDA AHVNGKVRGD SYQQVIDALT EYHASTVEHA DYELESVEKL LNLRKQIEGY VLGHPDSGRV EAMNSLLNQV NSRLEEVSVL AVSEQSIKAH DSFSRLYDQL DNANLKESKH LYLDGNGDFV TKGKGNLATI DQLGGSDAVL EKVKAAVTHE YGQVVADTIF ARLSANDLAK DGKGIDIAGL NKVHQAIEQH MSPVSATMYI WKPSDHSTLG HAALQIGQGR TQLEGQAAAD FNKQNYVSWW PLGSKSSNIR NIFNVATEDQ PDLKLRWSDF SQPAHQNDTL EHDMASEEND GFGLKDGETK LKRFIEKLNA AKGIDASYKD ASEGYASVLL GNPDMLASTG IPAHVFQPFV DQWNDTSYDM MDVANRFAEE LQKQAQASGD PALVEKRIDN VVRLFAERAL EEIEAFKASQ ADEGRVFRIN LEGLDVAAMQ AEWKRLSNDP DARYQLLTKN ASSTVAKVLK AGGADKLIGH TWRPKFGVWT PTELFNFGQA LQEAQLEIAA KKQSHQVTDV LDAL UniProtKB: Multifunctional-autoprocessing repeats-in-toxin |
-Macromolecule #2: Calmodulin
Macromolecule | Name: Calmodulin / type: protein_or_peptide / ID: 2 / Details: Q124E, "sequence conflict" / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Sequence | String: GAMADQLTEE QIAEFKEAFS LFDKDGDGTI TTKELGTVMR SLGQNPTEAE LQDMINEVDA DGNGTIDFPE FLTMMARKMK DTDSEEEIRE AFRVFDKDGN GYISAAELRH VMTNLGEKLT DEEVDQMIRE ADIDGDGQVN YEEFVQMMTA K UniProtKB: Calmodulin-2 |
-Macromolecule #3: Rac1
Macromolecule | Name: Rac1 / type: protein_or_peptide / ID: 3 / Details: single mutation, Q61L / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Sequence | String: GHMQAIKCVV VGDGAVGKTC LLISYTTNAF PGEYIPTVFD NYSANVMVDG KPVNLGLWDT AGLEDYDRLR PLSYPQTDVF LICFSLVSPA SFENVRAKWY PEVRHHCPNT PIILVGTKLD LRDDKDTIEK LKEKKLTPIT YPQGLAMAKE IGAVKYLECS ALTQRGLKTV FDEAIRAVL UniProtKB: Ras-related C3 botulinum toxin substrate 1 |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 0.75 mg/mL | ||||||||||||
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Buffer | pH: 7.5 Component:
Details: 50 mM HEPES-NaOH (pH 7.5), 150 mM NaCl, and 1% (v/v) glycerol | ||||||||||||
Grid | Model: Quantifoil R1.2/1.3 / Material: COPPER / Mesh: 300 / Support film - Material: CARBON / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE / Pretreatment - Time: 60 sec. / Pretreatment - Atmosphere: AIR | ||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 297 K / Instrument: FEI VITROBOT MARK IV | ||||||||||||
Details | This sample was monodisperse |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 2.2 µm / Nominal defocus min: 1.4000000000000001 µm |
Sample stage | Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |