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Yorodumi- EMDB-25524: Reconstruction of full-length Prex-1 (PtdIns(3,4,5)P3-dependent R... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-25524 | |||||||||
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Title | Reconstruction of full-length Prex-1 (PtdIns(3,4,5)P3-dependent Rac Exchanger 1) | |||||||||
Map data | ||||||||||
Sample |
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Keywords | guanine nucleotide exchange factor / metastasis / plasma membrane / Rho GTPase signalling / ONCOPROTEIN | |||||||||
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 / T cell differentiation / RHOG GTPase cycle / RHOA GTPase cycle / RAC2 GTPase cycle / RAC3 GTPase cycle / positive regulation of substrate adhesion-dependent cell spreading / viral release from host cell by cytolysis / RAC1 GTPase cycle / neutrophil chemotaxis / actin filament polymerization / peptidoglycan catabolic process / GTPase activator activity / guanyl-nucleotide exchange factor activity / dendritic shaft / phospholipid binding / G alpha (12/13) signalling events / cell wall macromolecule catabolic process / lysozyme / lysozyme activity / growth cone / host cell cytoplasm / positive regulation of cell migration / intracellular signal transduction / 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 | single particle reconstruction / cryo EM / Resolution: 4.2 Å | |||||||||
Authors | Lupton CJ / Bayly-Jones C | |||||||||
Funding support | Australia, 2 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_25524.map.gz | 13.1 MB | EMDB map data format | |
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Header (meta data) | emd-25524-v30.xml emd-25524.xml | 18.4 KB 18.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_25524_fsc.xml | 5.4 KB | Display | FSC data file |
Images | emd_25524.png | 51.8 KB | ||
Masks | emd_25524_msk_1.map | 14.5 MB | Mask map | |
Filedesc metadata | emd-25524.cif.gz | 6.5 KB | ||
Others | emd_25524_additional_1.map.gz emd_25524_half_map_1.map.gz emd_25524_half_map_2.map.gz | 7.4 MB 13.4 MB 13.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-25524 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-25524 | HTTPS FTP |
-Validation report
Summary document | emd_25524_validation.pdf.gz | 790.5 KB | Display | EMDB validaton report |
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Full document | emd_25524_full_validation.pdf.gz | 790 KB | Display | |
Data in XML | emd_25524_validation.xml.gz | 12.1 KB | Display | |
Data in CIF | emd_25524_validation.cif.gz | 15.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25524 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-25524 | HTTPS FTP |
-Related structure data
Related structure data | 7syfMC 7rx9C C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_25524.map.gz / Format: CCP4 / Size: 14.5 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.34564 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_25524_msk_1.map | ||||||||||||
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Density Histograms |
-Additional map: #1
File | emd_25524_additional_1.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_25524_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #1
File | emd_25524_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : full-length Prex-1 (PtdIns(3,4,5)P3-dependent Rac Exchanger 1)
Entire | Name: full-length Prex-1 (PtdIns(3,4,5)P3-dependent Rac Exchanger 1) |
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Components |
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-Supramolecule #1: full-length Prex-1 (PtdIns(3,4,5)P3-dependent Rac Exchanger 1)
Supramolecule | Name: full-length Prex-1 (PtdIns(3,4,5)P3-dependent Rac Exchanger 1) type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 191 KDa |
-Macromolecule #1: Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger ...
Macromolecule | Name: Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein,Endolysin chimera type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: lysozyme |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 191.462984 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGHHHHHHHH SSGSENLYFQ GRESERQLRL RLCVLNEILG TERDYVGTLR FLQSAFLHRI RQNVADSVEK GLTEENVKVL FSNIEDILE VHKDFLAALE YCLHPEPQSQ HELGNVFLKF KDKFCVYEEY CSNHEKALRL LVELNKIPTV RAFLLSCMLL G GRKTTDIP ...String: MGHHHHHHHH SSGSENLYFQ GRESERQLRL RLCVLNEILG TERDYVGTLR FLQSAFLHRI RQNVADSVEK GLTEENVKVL FSNIEDILE VHKDFLAALE YCLHPEPQSQ HELGNVFLKF KDKFCVYEEY CSNHEKALRL LVELNKIPTV RAFLLSCMLL G GRKTTDIP LEGYLLSPIQ RICKYPLLLK ELAKRTPGKH PDHPAVQSAL QAMKTVCSNI NETKRQMEKL EALEQLQSHI EG WEGSNLT DICTQLLLQG TLLKISAGNI QERAFFLFDN LLVYCKRKSN IFEMLRIDEG LRLKIYKDTE GYYTIGIGHL LTK SPSLNA AKSELDKAIG RNTNGVITKD EAEKLFNQDV DAAVRGILRN AKLKPVYDSL DAVRRAALIN MVFQMGETGV AGFT NSLRM LQQKRWDEAA VNLAKSRWYN QTPNRAKRVI TTFRTGTWDA YSLYIFRGRI NTEVMEVENV EDGTADYHSN GYTVT NGWK IHNTAKNKWF VCMAKTAEEK QKWLDAIIRE REQRESLKLG MERDAYVMIA EKGEKLYHMM MNKKVNLIKD RRRKLS TVP KCFLGNEFVA WLLEIGEISK TEEGVNLGQA LLENGIIHHV SDKHQFKNEQ VMYRFRYDDG TYKARSELED IMSKGVR LY CRLHSLYTPV IKDRDYHLKT YKSVLPGSKL VDWLLAQGDC QTREEAVALG VGLCNNGFMH HVLEKSEFRD ESQYFRFH A DEEMEGTSSK NKQLRNDFKL VENILAKRLL ILPQEEDYGF DIEEKNKAVV VKSVQRGSLA EVAGLQVGRK IYSINEDLV FLRPFSEVES ILNQSFCSRR PLRLLVATKA KEIIKIPDQP DTLCFQIRGA APPYVYAVGR GSEAMAAGLC AGQCILKVNG SNVMNDGAP EVLEHFQAFR SRREEALGLY QWIYHTHEDA QEARASQEAS TEDPSGEQAQ EEDQADSAFP LLSLGPRLSL C EDSPMVTL TVDNVHLEHG VVYEYVSTAG VRCHVLEKIV EPRGCFGLTA KILEAFAAND SVFVENCRRL MALSSAIVTM PH FEFRNIC DTKLESIGQR IACYQEFAAQ LKSRVSPPFK QAPLEPHPLC GLDFCPTNCH INLMEVSYPK TTPSVGRSFS IRF GRKPSL IGLDPEQGHL NPMSYTQHCI TTMAAPSWKC LPAAEGDPQG QGLHDGSFGP ASGTLGQEDR GLSFLLKQED REIQ DAYLQ LFTKLDVALK EMKQYVTQIN RLLSTITEPT SGGSCDTSDK QDKLHGCLEH LFNQVDSINA LLKGPVMSRA FEETK HFPM NHSLQEFKQK EECTIRGRSL IQISIQEDPW NLPNSIKTLV DNIQRYVEDG KNQLLLALLK CTDTELQLRR DAIFCQ ALV AAVCTFSEQL LAALGYRYNN NGEYEESSRD ASRKWLEQVA ATGVLLHCQS LLSPATVKEE RTMLEDIWVT LSELDNV TF SFKQLDENYV ANTNVFYHIE GSRQALKVIF YLDSYHFSKL PSRLEGGASL RLHTALFTKV LENVEGLPSP GSQAAEDL Q QDINAQSLEK VQQYYRKLRA FYLERSNLPT DASTTAVKID QLIRPINALD ELCRLMKSFV HPKPGAAGSV GAGLIPISS ELCYRLGACQ MVMCGTGMQR STLSVSLEQA AILARSHGLL PKCIMQATDI MRKQGPRVEI LAKNLRVKDQ MPQGAPRLYR LCQPPVDGD L UniProtKB: Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein, Endolysin, Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein, Phosphatidylinositol ...UniProtKB: Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein, Endolysin, Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein, Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 0.18 mg/mL |
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Buffer | pH: 8 |
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |