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Yorodumi- PDB-7syf: Reconstruction of full-length Prex-1 (PtdIns(3,4,5)P3-dependent R... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7syf | |||||||||
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Title | Reconstruction of full-length Prex-1 (PtdIns(3,4,5)P3-dependent Rac Exchanger 1) | |||||||||
Components | Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein,Endolysin chimera | |||||||||
Keywords | ONCOPROTEIN / guanine nucleotide exchange factor / metastasis / plasma membrane / Rho GTPase signalling | |||||||||
Function / homology | Function and homology information regulation of signaling / regulation of dendrite development / neutrophil activation / regulation of actin filament polymerization / regulation of small GTPase mediated signal transduction / RHOB GTPase cycle / superoxide metabolic process / NRAGE signals death through JNK / RHOC GTPase cycle / RHOJ GTPase cycle ...regulation of signaling / regulation of dendrite development / neutrophil activation / regulation of actin filament polymerization / regulation of small GTPase mediated signal transduction / RHOB GTPase cycle / superoxide metabolic process / NRAGE signals death through JNK / RHOC GTPase cycle / RHOJ GTPase cycle / RHOQ GTPase cycle / CDC42 GTPase cycle / RHOG GTPase cycle / T cell differentiation / RHOA GTPase cycle / RAC3 GTPase cycle / RAC2 GTPase cycle / positive regulation of substrate adhesion-dependent cell spreading / viral release from host cell by cytolysis / RAC1 GTPase cycle / actin filament polymerization / GTPase activator activity / guanyl-nucleotide exchange factor activity / peptidoglycan catabolic process / neutrophil chemotaxis / dendritic shaft / phospholipid binding / G alpha (12/13) signalling events / cell wall macromolecule catabolic process / lysozyme / lysozyme activity / growth cone / host cell cytoplasm / intracellular signal transduction / positive regulation of cell migration / defense response to bacterium / G protein-coupled receptor signaling pathway / perinuclear region of cytoplasm / enzyme binding / plasma membrane / cytosol Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.2 Å | |||||||||
Authors | Lupton, C.J. / Bayly-Jones, C. / Ellisdon, A.M. | |||||||||
Funding support | Australia, 2items
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Citation | Journal: Nat Struct Mol Biol / Year: 2022 Title: Structure of the metastatic factor P-Rex1 reveals a two-layered autoinhibitory mechanism. Authors: Yong-Gang Chang / Christopher J Lupton / Charles Bayly-Jones / Alastair C Keen / Laura D'Andrea / Christina M Lucato / Joel R Steele / Hari Venugopal / Ralf B Schittenhelm / James C ...Authors: Yong-Gang Chang / Christopher J Lupton / Charles Bayly-Jones / Alastair C Keen / Laura D'Andrea / Christina M Lucato / Joel R Steele / Hari Venugopal / Ralf B Schittenhelm / James C Whisstock / Michelle L Halls / Andrew M Ellisdon / Abstract: P-Rex (PI(3,4,5)P-dependent Rac exchanger) guanine nucleotide exchange factors potently activate Rho GTPases. P-Rex guanine nucleotide exchange factors are autoinhibited, synergistically activated by ...P-Rex (PI(3,4,5)P-dependent Rac exchanger) guanine nucleotide exchange factors potently activate Rho GTPases. P-Rex guanine nucleotide exchange factors are autoinhibited, synergistically activated by Gβγ and PI(3,4,5)P binding and dysregulated in cancer. Here, we use X-ray crystallography, cryogenic electron microscopy and crosslinking mass spectrometry to determine the structural basis of human P-Rex1 autoinhibition. P-Rex1 has a bipartite structure of N- and C-terminal modules connected by a C-terminal four-helix bundle that binds the N-terminal Pleckstrin homology (PH) domain. In the N-terminal module, the Dbl homology (DH) domain catalytic surface is occluded by the compact arrangement of the DH-PH-DEP1 domains. Structural analysis reveals a remarkable conformational transition to release autoinhibition, requiring a 126° opening of the DH domain hinge helix. The off-axis position of Gβγ and PI(3,4,5)P binding sites further suggests a counter-rotation of the P-Rex1 halves by 90° facilitates PH domain uncoupling from the four-helix bundle, releasing the autoinhibited DH domain to drive Rho GTPase signaling. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7syf.cif.gz | 264.5 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7syf.ent.gz | 203.7 KB | Display | PDB format |
PDBx/mmJSON format | 7syf.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/sy/7syf ftp://data.pdbj.org/pub/pdb/validation_reports/sy/7syf | HTTPS FTP |
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-Related structure data
Related structure data | 25524MC 7rx9C M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 191462.984 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PREX1, KIAA1415, e, T4Tp126 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q8TCU6, UniProt: D9IEF7, lysozyme |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: full-length Prex-1 (PtdIns(3,4,5)P3-dependent Rac Exchanger 1) Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
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Molecular weight | Value: 0.191 MDa / Experimental value: YES |
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 8 |
Specimen | Conc.: 0.18 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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Symmetry | Point symmetry: C1 (asymmetric) |
3D reconstruction | Resolution: 4.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 123896 / Symmetry type: POINT |