[English] 日本語
Yorodumi
- PDB-8xep: Crystal structure of a Legionella pneumophila type IV effector in... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8xep
TitleCrystal structure of a Legionella pneumophila type IV effector in complex with ubiquitin
Components
  • Type IV effector MavL
  • Ubiquitin
KeywordsHYDROLASE / Legionella pneumophila / type IV effector / ubiquitin / ARHs
Function / homology
Function and homology information


ADP-D-ribose binding / hypothalamus gonadotrophin-releasing hormone neuron development / female meiosis I / positive regulation of protein monoubiquitination / fat pad development / seminiferous tubule development / mitochondrion transport along microtubule / female gonad development / male meiosis I / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator ...ADP-D-ribose binding / hypothalamus gonadotrophin-releasing hormone neuron development / female meiosis I / positive regulation of protein monoubiquitination / fat pad development / seminiferous tubule development / mitochondrion transport along microtubule / female gonad development / male meiosis I / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / energy homeostasis / neuron projection morphogenesis / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Prevention of phagosomal-lysosomal fusion / Endosomal Sorting Complex Required For Transport (ESCRT) / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / Negative regulation of FLT3 / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / Constitutive Signaling by NOTCH1 HD Domain Mutants / NOTCH2 Activation and Transmission of Signal to the Nucleus / TICAM1,TRAF6-dependent induction of TAK1 complex / regulation of proteasomal protein catabolic process / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / regulation of neuron apoptotic process / Downregulation of ERBB4 signaling / APC-Cdc20 mediated degradation of Nek2A / Regulation of FZD by ubiquitination / p75NTR recruits signalling complexes / InlA-mediated entry of Listeria monocytogenes into host cells / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / NF-kB is activated and signals survival / TRAF6-mediated induction of TAK1 complex within TLR4 complex / Regulation of pyruvate metabolism / positive regulation of protein ubiquitination / Pexophagy / Downregulation of ERBB2:ERBB3 signaling / Regulation of innate immune responses to cytosolic DNA / NRIF signals cell death from the nucleus / Regulation of PTEN localization / regulation of mitochondrial membrane potential / VLDLR internalisation and degradation / Activated NOTCH1 Transmits Signal to the Nucleus / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by REV1 / TICAM1, RIP1-mediated IKK complex recruitment / Regulation of BACH1 activity / Translesion synthesis by POLK / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / InlB-mediated entry of Listeria monocytogenes into host cell / MAP3K8 (TPL2)-dependent MAPK1/3 activation / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Downregulation of TGF-beta receptor signaling / Translesion synthesis by POLI / Josephin domain DUBs / Gap-filling DNA repair synthesis and ligation in GG-NER / IKK complex recruitment mediated by RIP1 / PINK1-PRKN Mediated Mitophagy / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / TNFR1-induced NF-kappa-B signaling pathway / Regulation of activated PAK-2p34 by proteasome mediated degradation / TCF dependent signaling in response to WNT / Regulation of NF-kappa B signaling / activated TAK1 mediates p38 MAPK activation / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / NOTCH3 Activation and Transmission of Signal to the Nucleus / Regulation of signaling by CBL / Negative regulators of DDX58/IFIH1 signaling / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Asymmetric localization of PCP proteins / Fanconi Anemia Pathway / Negative regulation of FGFR3 signaling / Ubiquitin-dependent degradation of Cyclin D / Peroxisomal protein import / Deactivation of the beta-catenin transactivating complex / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Stabilization of p53 / AUF1 (hnRNP D0) binds and destabilizes mRNA / TNFR2 non-canonical NF-kB pathway / Negative regulation of FGFR2 signaling / Negative regulation of FGFR4 signaling / Downregulation of SMAD2/3:SMAD4 transcriptional activity / Negative regulation of FGFR1 signaling / Termination of translesion DNA synthesis / Assembly of the pre-replicative complex / Vpu mediated degradation of CD4
Similarity search - Function
: / Macrodomain effector MavL / : / Ubiquitin domain signature. / Ubiquitin conserved site / Ubiquitin domain / Ubiquitin family / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Ubiquitin-like domain superfamily
Similarity search - Domain/homology
Polyubiquitin-B / Macrodomain effector MavL domain-containing protein
Similarity search - Component
Biological speciesLegionella pneumophila subsp. pneumophila str. Philadelphia 1 (bacteria)
Homo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.95 Å
AuthorsTan, J.X. / Wang, X.F. / Zhou, Y. / Zhu, Y.Q.
Funding support China, 2items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)81925024 China
Ministry of Science and Technology (MoST, China)2017YFA0503900 China
CitationJournal: Nature / Year: 2024
Title: Legionella effector LnaB is a phosphoryl-AMPylase that impairs phosphosignalling.
Authors: Ting Wang / Xiaonan Song / Jiaxing Tan / Wei Xian / Xingtong Zhou / Mingru Yu / Xiaofei Wang / Yan Xu / Ting Wu / Keke Yuan / Yu Ran / Bing Yang / Gaofeng Fan / Xiaoyun Liu / Yan Zhou / Yongqun Zhu /
Abstract: AMPylation is a post-translational modification in which AMP is added to the amino acid side chains of proteins. Here we show that, with ATP as the ligand and actin as the host activator, the ...AMPylation is a post-translational modification in which AMP is added to the amino acid side chains of proteins. Here we show that, with ATP as the ligand and actin as the host activator, the effector protein LnaB of Legionella pneumophila exhibits AMPylase activity towards the phosphoryl group of phosphoribose on PR-Ub that is generated by the SidE family of effectors, and deubiquitinases DupA and DupB in an E1- and E2-independent ubiquitination process. The product of LnaB is further hydrolysed by an ADP-ribosylhydrolase, MavL, to Ub, thereby preventing the accumulation of PR-Ub and ADPR-Ub and protecting canonical ubiquitination in host cells. LnaB represents a large family of AMPylases that adopt a common structural fold, distinct from those of the previously known AMPylases, and LnaB homologues are found in more than 20 species of bacterial pathogens. Moreover, LnaB also exhibits robust phosphoryl AMPylase activity towards phosphorylated residues and produces unique ADPylation modifications in proteins. During infection, LnaB AMPylates the conserved phosphorylated tyrosine residues in the activation loop of the Src family of kinases, which dampens downstream phosphorylation signalling in the host. Structural studies reveal the actin-dependent activation and catalytic mechanisms of the LnaB family of AMPylases. This study identifies, to our knowledge, an unprecedented molecular regulation mechanism in bacterial pathogenesis and protein phosphorylation.
History
DepositionDec 12, 2023Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0May 1, 2024Provider: repository / Type: Initial release
Revision 1.1Jul 3, 2024Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Jul 24, 2024Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.identifier_ORCID

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Type IV effector MavL
B: Ubiquitin
C: Ubiquitin
D: Type IV effector MavL
hetero molecules


Theoretical massNumber of molelcules
Total (without water)118,8806
Polymers118,6884
Non-polymers1922
Water00
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area6450 Å2
ΔGint-55 kcal/mol
Surface area34300 Å2
MethodPISA
Unit cell
Length a, b, c (Å)200.951, 56.696, 100.238
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number18
Space group name H-MP21212

-
Components

#1: Protein Type IV effector MavL


Mass: 50767.090 Da / Num. of mol.: 2 / Mutation: C226A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Legionella pneumophila subsp. pneumophila str. Philadelphia 1 (bacteria)
Gene: lpg2526 / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: Q5ZSJ1
#2: Protein Ubiquitin


Mass: 8576.831 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: UBB / Production host: Escherichia coli BL21(DE3) (bacteria) / References: UniProt: P0CG47
#3: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4 / Feature type: SUBJECT OF INVESTIGATION
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.41 Å3/Da / Density % sol: 48.87 %
Crystal growTemperature: 289 K / Method: vapor diffusion, hanging drop / pH: 6
Details: 100 mM sodium acetate, pH 6.0, 160 mM ammonium sulfate, 21% PEG 4000, 20% glycerol

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL17U1 / Wavelength: 0.979183 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Nov 19, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979183 Å / Relative weight: 1
ReflectionResolution: 2.95→49.38 Å / Num. obs: 25049 / % possible obs: 99.8 % / Redundancy: 5.9 % / CC1/2: 0.996 / Rmerge(I) obs: 0.139 / Rpim(I) all: 0.062 / Rrim(I) all: 0.153 / Χ2: 0.98 / Net I/σ(I): 10.8 / Num. measured all: 146652
Reflection shellResolution: 2.95→3.12 Å / % possible obs: 99.2 % / Redundancy: 6 % / Rmerge(I) obs: 0.831 / Num. measured all: 23533 / Num. unique obs: 3946 / CC1/2: 0.881 / Rpim(I) all: 0.368 / Rrim(I) all: 0.91 / Χ2: 1.01 / Net I/σ(I) obs: 2.2

-
Processing

Software
NameVersionClassification
PHENIX(1.19_4092: ???)refinement
Aimlessdata scaling
XDSdata reduction
PHASERphasing
Cootmodel building
PDB_EXTRACTdata extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.95→19.19 Å / SU ML: 0.33 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 25.24 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2275 1223 4.94 %
Rwork0.2177 --
obs0.2182 24771 99.74 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.95→19.19 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6914 0 10 0 6924
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0037072
X-RAY DIFFRACTIONf_angle_d0.5829575
X-RAY DIFFRACTIONf_dihedral_angle_d17.1722633
X-RAY DIFFRACTIONf_chiral_restr0.0431048
X-RAY DIFFRACTIONf_plane_restr0.0051239
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.95-3.070.39031340.36352545X-RAY DIFFRACTION100
3.07-3.210.34391230.33632585X-RAY DIFFRACTION99
3.21-3.370.31451310.2662574X-RAY DIFFRACTION100
3.37-3.590.25011230.26072609X-RAY DIFFRACTION100
3.59-3.860.23521610.22122569X-RAY DIFFRACTION100
3.86-4.240.2121280.20072599X-RAY DIFFRACTION100
4.24-4.850.16981360.18122630X-RAY DIFFRACTION100
4.85-6.080.19461300.19592668X-RAY DIFFRACTION100
6.08-19.190.21221570.18562769X-RAY DIFFRACTION100

+
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