[English] 日本語
Yorodumi
- PDB-8t7c: Crystal structure of human phospholipase C gamma 2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8t7c
TitleCrystal structure of human phospholipase C gamma 2
Components1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2
KeywordsHYDROLASE / Phospholipase C gamma 2 / autoinhibition / signaling / lipid metabolism
Function / homology
Function and homology information


inositol trisphosphate biosynthetic process / regulation of calcineurin-NFAT signaling cascade / follicular B cell differentiation / positive regulation of dendritic cell cytokine production / phosphoinositide phospholipase C / antifungal innate immune response / cellular response to lectin / positive regulation of interleukin-23 production / phosphorylation-dependent protein binding / Toll Like Receptor 4 (TLR4) Cascade ...inositol trisphosphate biosynthetic process / regulation of calcineurin-NFAT signaling cascade / follicular B cell differentiation / positive regulation of dendritic cell cytokine production / phosphoinositide phospholipase C / antifungal innate immune response / cellular response to lectin / positive regulation of interleukin-23 production / phosphorylation-dependent protein binding / Toll Like Receptor 4 (TLR4) Cascade / positive regulation of cell cycle G1/S phase transition / phosphatidylinositol metabolic process / response to yeast / phosphatidylinositol-4,5-bisphosphate phospholipase C activity / cell activation / positive regulation of phagocytosis, engulfment / Erythropoietin activates Phospholipase C gamma (PLCG) / C-type glycerophospholipase activity / phosphatidylinositol biosynthetic process / programmed cell death / phospholipid catabolic process / macrophage activation involved in immune response / cellular response to lipid / regulation of canonical NF-kappaB signal transduction / positive regulation of neuroinflammatory response / negative regulation of programmed cell death / positive regulation of macrophage cytokine production / toll-like receptor signaling pathway / phosphatidylinositol-mediated signaling / Dectin-2 family / Fc-epsilon receptor signaling pathway / stimulatory C-type lectin receptor signaling pathway / intracellular vesicle / Synthesis of IP3 and IP4 in the cytosol / positive regulation of reactive oxygen species biosynthetic process / positive regulation of NLRP3 inflammasome complex assembly / B cell activation / positive regulation of intracellular signal transduction / Generation of second messenger molecules / regulation of lipid metabolic process / positive regulation of receptor internalization / positive regulation of epithelial cell migration / positive regulation of interleukin-10 production / Role of phospholipids in phagocytosis / response to axon injury / GPVI-mediated activation cascade / positive regulation of type I interferon production / phosphotyrosine residue binding / release of sequestered calcium ion into cytosol / positive regulation of interleukin-12 production / FCERI mediated Ca+2 mobilization / positive regulation of calcium-mediated signaling / positive regulation of interleukin-2 production / FCGR3A-mediated IL10 synthesis / cellular response to calcium ion / B cell differentiation / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / lipopolysaccharide-mediated signaling pathway / protein tyrosine kinase binding / B cell receptor signaling pathway / FCERI mediated MAPK activation / calcium-mediated signaling / platelet activation / positive regulation of interleukin-6 production / CLEC7A (Dectin-1) signaling / ruffle membrane / Wnt signaling pathway / positive regulation of tumor necrosis factor production / Signaling by CSF1 (M-CSF) in myeloid cells / DAP12 signaling / T cell receptor signaling pathway / scaffold protein binding / Potential therapeutics for SARS / positive regulation of canonical NF-kappaB signal transduction / positive regulation of MAPK cascade / intracellular signal transduction / membrane raft / positive regulation of gene expression / protein kinase binding / perinuclear region of cytoplasm / extracellular exosome / plasma membrane / cytoplasm / cytosol
Similarity search - Function
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2, SH3 domain / Phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma / PLC-gamma, C-terminal SH2 domain / PLC-gamma, N-terminal SH2 domain / : / PLCG EF-hand motif 2 / Pleckstrin homology domain / Phosphoinositide phospholipase C family / Phospholipase C, phosphatidylinositol-specific, Y domain / Phosphatidylinositol-specific phospholipase C, Y domain ...1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2, SH3 domain / Phosphatidylinositol-4, 5-bisphosphate phosphodiesterase gamma / PLC-gamma, C-terminal SH2 domain / PLC-gamma, N-terminal SH2 domain / : / PLCG EF-hand motif 2 / Pleckstrin homology domain / Phosphoinositide phospholipase C family / Phospholipase C, phosphatidylinositol-specific, Y domain / Phosphatidylinositol-specific phospholipase C, Y domain / Phosphatidylinositol-specific phospholipase Y-box domain profile. / Phospholipase C, catalytic domain (part); domain Y / Phosphatidylinositol-specific phospholipase C, X domain / Phosphatidylinositol-specific phospholipase C, X domain / Phospholipase C, catalytic domain (part); domain X / Phosphatidylinositol-specific phospholipase X-box domain profile. / PLC-like phosphodiesterase, TIM beta/alpha-barrel domain superfamily / Protein kinase C conserved region 2 (CalB) / C2 domain / C2 domain / C2 domain profile. / C2 domain superfamily / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / Src homology 3 domains / SH2 domain superfamily / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / EF-hand domain pair / PH-like domain superfamily
Similarity search - Domain/homology
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.55 Å
AuthorsChen, Y. / Choi, H. / Zhuang, N. / Hu, L. / Qian, D. / Wang, J.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Sci Adv / Year: 2024
Title: The crystal and cryo-EM structures of PLCγ2 reveal dynamic interdomain recognitions in autoinhibition.
Authors: Young-Cheul Shin / Ashlee Marie Plummer-Medeiros / Alison Mungenast / Hyeong-Wook Choi / Karen TenDyke / Xiaojie Zhu / Jennifer Shepard / Kristen Sanders / Ningning Zhuang / Liang Hu / ...Authors: Young-Cheul Shin / Ashlee Marie Plummer-Medeiros / Alison Mungenast / Hyeong-Wook Choi / Karen TenDyke / Xiaojie Zhu / Jennifer Shepard / Kristen Sanders / Ningning Zhuang / Liang Hu / Dongming Qian / Kangkang Song / Chen Xu / John Wang / Suresh B Poda / Maofu Liao / Yu Chen /
Abstract: Phospholipase C gamma 2 (PLCγ2) plays important roles in cell signaling downstream of various membrane receptors. PLCγ2 contains a multidomain inhibitory region critical for its regulation, while ...Phospholipase C gamma 2 (PLCγ2) plays important roles in cell signaling downstream of various membrane receptors. PLCγ2 contains a multidomain inhibitory region critical for its regulation, while it has remained unclear how these domains contribute to PLCγ2 activity modulation. Here we determined three structures of human PLCγ2 in autoinhibited states, which reveal dynamic interactions at the autoinhibition interface, involving the conformational flexibility of the Src homology 3 (SH3) domain in the inhibitory region, and its previously unknown interaction with a carboxyl-terminal helical domain in the core region. We also determined a structure of PLCγ2 bound to the kinase domain of fibroblast growth factor receptor 1 (FGFR1), which demonstrates the recognition of FGFR1 by the nSH2 domain in the inhibitory region of PLCγ2. Our results provide structural insights into PLCγ2 regulation that will facilitate future mechanistic studies to understand the entire activation process.
History
DepositionJun 20, 2023Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 26, 2024Provider: repository / Type: Initial release
Revision 1.1Dec 11, 2024Group: Database references / Structure summary / Category: citation / citation_author / pdbx_entry_details
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)136,1643
Polymers136,0611
Non-polymers1022
Water3,423190
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)78.340, 97.140, 180.920
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 / Phosphoinositide phospholipase C-gamma-2 / Phospholipase C-IV / PLC-IV / Phospholipase C-gamma-2 / PLC-gamma-2


Mass: 136061.469 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PLCG2 / Production host: Trichoplusia ni (cabbage looper)
References: UniProt: P16885, phosphoinositide phospholipase C
#2: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Ca / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 190 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.53 Å3/Da / Density % sol: 51.38 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / Details: 0.1 M Magnesium Formate, 15 % w/v PEG 3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL19U1 / Wavelength: 0.97853 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Jun 1, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97853 Å / Relative weight: 1
ReflectionResolution: 2.55→48.62 Å / Num. obs: 45784 / % possible obs: 100 % / Redundancy: 6.6 % / CC1/2: 0.992 / Net I/σ(I): 8.7
Reflection shellResolution: 2.55→2.64 Å / Num. unique obs: 4415 / CC1/2: 0.789

-
Processing

Software
NameVersionClassification
REFMAC5.8.0267refinement
XDSdata reduction
PHASERphasing
Aimlessdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6PBC

6pbc


Resolution: 2.55→48.62 Å / Cor.coef. Fo:Fc: 0.929 / Cor.coef. Fo:Fc free: 0.889 / SU B: 13.062 / SU ML: 0.275 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.545 / ESU R Free: 0.322 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2816 2243 4.9 %RANDOM
Rwork0.2268 ---
obs0.2295 43414 99.67 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 158.21 Å2 / Biso mean: 56.755 Å2 / Biso min: 20.81 Å2
Baniso -1Baniso -2Baniso -3
1--2.71 Å20 Å2-0 Å2
2--0 Å20 Å2
3---2.71 Å2
Refinement stepCycle: final / Resolution: 2.55→48.62 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms8198 0 5 190 8393
Biso mean--49.75 41.74 -
Num. residues----1001
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0030.0138406
X-RAY DIFFRACTIONr_bond_other_d0.0030.0157905
X-RAY DIFFRACTIONr_angle_refined_deg1.2451.64811348
X-RAY DIFFRACTIONr_angle_other_deg1.0681.58218254
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.9615998
X-RAY DIFFRACTIONr_dihedral_angle_2_deg31.30522.008478
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.593151522
X-RAY DIFFRACTIONr_dihedral_angle_4_deg15.8521562
X-RAY DIFFRACTIONr_chiral_restr0.0450.21069
X-RAY DIFFRACTIONr_gen_planes_refined0.0030.029389
X-RAY DIFFRACTIONr_gen_planes_other0.0010.021995
X-RAY DIFFRACTIONr_mcbond_it2.4265.9384006
X-RAY DIFFRACTIONr_mcbond_other2.4255.9394003
X-RAY DIFFRACTIONr_mcangle_it4.1478.8984998
LS refinement shellResolution: 2.55→2.616 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.396 170 -
Rwork0.333 3168 -
all-3338 -
obs--99.88 %

+
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