[English] 日本語
Yorodumi
- PDB-7dpa: Cryo-EM structure of the human ELMO1-DOCK5-Rac1 complex -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7dpa
TitleCryo-EM structure of the human ELMO1-DOCK5-Rac1 complex
Components
  • Dedicator of cytokinesis protein 5
  • Engulfment and cell motility protein 1
  • Ras-related C3 botulinum toxin substrate 1
KeywordsSIGNALING PROTEIN / ELMO / DOCK / GEF / GTPASE / RHO / RAC
Function / homology
Function and homology information


regulation of vasculogenesis / guanyl nucleotide exchange factor activator activity / negative regulation of vascular associated smooth muscle contraction / 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 ...regulation of vasculogenesis / guanyl nucleotide exchange factor activator activity / negative regulation of vascular associated smooth muscle contraction / 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 / Rac protein signal transduction / regulation of hydrogen peroxide metabolic process / Inactivation of CDC42 and RAC1 / engulfment of apoptotic cell / guanyl-nucleotide exchange factor complex / superoxide anion generation / SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion / WNT5:FZD7-mediated leishmania damping / respiratory burst / motor neuron axon guidance / ruffle organization / myoblast fusion / positive regulation of bicellular tight junction assembly / midbrain dopaminergic neuron differentiation / GTP-dependent protein binding / 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 / hepatocyte growth factor receptor signaling pathway / PCP/CE pathway / RHO GTPases activate KTN1 / sphingosine-1-phosphate receptor signaling pathway / forebrain development / MET activates RAP1 and RAC1 / DCC mediated attractive signaling / positive regulation of vascular associated smooth muscle cell migration / Sema4D mediated inhibition of cell attachment and migration / Azathioprine ADME / Ephrin signaling / lamellipodium assembly / positive regulation of neutrophil chemotaxis / CD28 dependent Vav1 pathway / positive regulation of ruffle assembly / Wnt signaling pathway, planar cell polarity pathway / phagocytosis, engulfment / podosome / regulation of receptor signaling pathway via JAK-STAT / NRAGE signals death through JNK / Rho GDP-dissociation inhibitor binding / Activation of RAC1 downstream of NMDARs / small GTPase-mediated signal transduction / positive regulation of Rho protein signal transduction / pericentriolar material / positive regulation of epithelial cell migration / establishment or maintenance of cell polarity / semaphorin-plexin signaling pathway / RHO GTPases activate PAKs / Sema3A PAK dependent Axon repulsion / RHOG GTPase cycle / 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 / anatomical structure morphogenesis / positive regulation of stress fiber assembly / regulation of synaptic vesicle endocytosis / RHO GTPases Activate WASPs and WAVEs / substrate adhesion-dependent cell spreading / positive regulation of lamellipodium assembly / positive regulation of substrate adhesion-dependent cell spreading / 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 / GTPase activator activity / positive regulation of endothelial cell migration / actin filament organization / guanyl-nucleotide exchange factor activity / 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
Similarity search - Function
Dedicator of cytokinesis protein 5 / : / : / Dedicator of cytokinesis, N-terminal domain / Dedicator of cytokinesis, N-terminal, subdomain 1 / : / DOCK N-terminus / Dedicator of cytokinesis (DOCK) TPR region / ELMO protein N-terminal Ras-binding domain / ELMO domain ...Dedicator of cytokinesis protein 5 / : / : / Dedicator of cytokinesis, N-terminal domain / Dedicator of cytokinesis, N-terminal, subdomain 1 / : / DOCK N-terminus / Dedicator of cytokinesis (DOCK) TPR region / ELMO protein N-terminal Ras-binding domain / ELMO domain / ELMO, armadillo-like helical domain / : / ELMO/CED-12 family / ELMO, armadillo-like helical domain / ELMO domain profile. / Pleckstrin homology 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 / Pleckstrin homology domain / SH3 domain / Rho (Ras homology) subfamily of Ras-like small GTPases / Ras subfamily of RAS small GTPases / Small GTPase / Ras family / Src homology 3 domains / Rab subfamily of small GTPases / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / Armadillo-like helical / Small GTP-binding protein domain / PH-like domain superfamily / Armadillo-type fold / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Ras-related C3 botulinum toxin substrate 1 / Engulfment and cell motility protein 1 / Dedicator of cytokinesis protein 5
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.8 Å
AuthorsKukimoto-Niino, M. / Katsura, K. / Kaushik, R. / Ehara, H. / Yokoyama, T. / Uchikubo-Kamo, T. / Mishima-Tsumagari, C. / Yonemochi, M. / Ikeda, M. / Hanada, K. ...Kukimoto-Niino, M. / Katsura, K. / Kaushik, R. / Ehara, H. / Yokoyama, T. / Uchikubo-Kamo, T. / Mishima-Tsumagari, C. / Yonemochi, M. / Ikeda, M. / Hanada, K. / Zhang, K.Y.J. / Shirouzu, M.
CitationJournal: Sci Adv / Year: 2021
Title: Cryo-EM structure of the human ELMO1-DOCK5-Rac1 complex.
Authors: Mutsuko Kukimoto-Niino / Kazushige Katsura / Rahul Kaushik / Haruhiko Ehara / Takeshi Yokoyama / Tomomi Uchikubo-Kamo / Reiko Nakagawa / Chiemi Mishima-Tsumagari / Mayumi Yonemochi / Mariko ...Authors: Mutsuko Kukimoto-Niino / Kazushige Katsura / Rahul Kaushik / Haruhiko Ehara / Takeshi Yokoyama / Tomomi Uchikubo-Kamo / Reiko Nakagawa / Chiemi Mishima-Tsumagari / Mayumi Yonemochi / Mariko Ikeda / Kazuharu Hanada / Kam Y J Zhang / Mikako Shirouzu /
Abstract: The dedicator of cytokinesis (DOCK) family of guanine nucleotide exchange factors (GEFs) promotes cell motility, phagocytosis, and cancer metastasis through activation of Rho guanosine ...The dedicator of cytokinesis (DOCK) family of guanine nucleotide exchange factors (GEFs) promotes cell motility, phagocytosis, and cancer metastasis through activation of Rho guanosine triphosphatases. Engulfment and cell motility (ELMO) proteins are binding partners of DOCK and regulate Rac activation. Here, we report the cryo-electron microscopy structure of the active ELMO1-DOCK5 complex bound to Rac1 at 3.8-Å resolution. The C-terminal region of ELMO1, including the pleckstrin homology (PH) domain, aids in the binding of the catalytic DOCK homology region 2 (DHR-2) domain of DOCK5 to Rac1 in its nucleotide-free state. A complex α-helical scaffold between ELMO1 and DOCK5 stabilizes the binding of Rac1. Mutagenesis studies revealed that the PH domain of ELMO1 enhances the GEF activity of DOCK5 through specific interactions with Rac1. The structure provides insights into how ELMO modulates the biochemical activity of DOCK and how Rac selectivity is achieved by ELMO.
History
DepositionDec 18, 2020Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Aug 4, 2021Provider: repository / Type: Initial release
Revision 1.1Mar 27, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-30802
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Dedicator of cytokinesis protein 5
B: Ras-related C3 botulinum toxin substrate 1
C: Engulfment and cell motility protein 1
D: Dedicator of cytokinesis protein 5
E: Ras-related C3 botulinum toxin substrate 1
F: Engulfment and cell motility protein 1


Theoretical massNumber of molelcules
Total (without water)592,1486
Polymers592,1486
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area19280 Å2
ΔGint-114 kcal/mol
Surface area205930 Å2

-
Components

#1: Protein Dedicator of cytokinesis protein 5


Mass: 191492.125 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: DOCK5 / Production host: Homo sapiens (human) / References: UniProt: Q9H7D0
#2: Protein Ras-related C3 botulinum toxin substrate 1 / Cell migration-inducing gene 5 protein / Ras-like protein TC25 / p21-Rac1


Mass: 20244.258 Da / Num. of mol.: 2 / Mutation: G15A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RAC1, TC25, MIG5 / Production host: Escherichia coli (E. coli) / References: UniProt: P63000, small monomeric GTPase
#3: Protein Engulfment and cell motility protein 1 / Protein ced-12 homolog


Mass: 84337.719 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ELMO1, KIAA0281 / Production host: Homo sapiens (human) / References: UniProt: Q92556

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: ELMO1-DOCK5-Rac1 / 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
Specimen supportGrid material: COPPER / Grid mesh size: 300 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationCryogen name: ETHANE / Humidity: 100 %

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: OTHER
Electron lensMode: BRIGHT FIELD / Calibrated magnification: 105000 X / Calibrated defocus min: 0.5 nm / Calibrated defocus max: 3 nm
Image recordingElectron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

EM software
IDNameVersionCategory
1RELION3particle selection
4CTFFIND4CTF correction
7Cootmodel fitting
9RELION3initial Euler assignment
10RELION3final Euler assignment
11RELION3classification
12RELION3.13D reconstruction
13PHENIX1.18.2model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 2145777
SymmetryPoint symmetry: C2 (2 fold cyclic)
3D reconstructionResolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 149846 / Num. of class averages: 1 / Symmetry type: POINT

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more