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- PDB-2jri: Solution structure of the Josephin domain of Ataxin-3 in complex ... -

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Basic information

Entry
Database: PDB / ID: 2jri
TitleSolution structure of the Josephin domain of Ataxin-3 in complex with ubiquitin molecule.
Components
  • Ataxin-3Ataxin 3
  • UBC protein
KeywordsHYDROLASE/SIGNALING PROTEIN / di-ubiquitin / Lys48-linked / Josephin domain of ataxin-3 / spinocerebellar ataxia type 3 protein / Alternative splicing / Hydrolase / Neurodegeneration / Nucleus / Phosphorylation / Polymorphism / Transcription / Transcription regulation / Triplet repeat expansion / HYDROLASE-SIGNALING PROTEIN COMPLEX
Function / homology
Function and homology information


protein localization to cytosolic proteasome complex / regulation of cell-substrate adhesion / positive regulation of ERAD pathway / monoubiquitinated protein deubiquitination / intermediate filament cytoskeleton organization / protein K48-linked deubiquitination / nuclear inclusion body / positive regulation of ubiquitin-dependent protein catabolic process / cellular response to misfolded protein / protein K63-linked deubiquitination ...protein localization to cytosolic proteasome complex / regulation of cell-substrate adhesion / positive regulation of ERAD pathway / monoubiquitinated protein deubiquitination / intermediate filament cytoskeleton organization / protein K48-linked deubiquitination / nuclear inclusion body / positive regulation of ubiquitin-dependent protein catabolic process / cellular response to misfolded protein / protein K63-linked deubiquitination / K48-linked deubiquitinase activity / exploration behavior / K63-linked deubiquitinase activity / protein quality control for misfolded or incompletely synthesized proteins / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / negative regulation of TORC1 signaling / Prevention of phagosomal-lysosomal fusion / 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 / Membrane binding and targetting of GAG proteins / Constitutive Signaling by NOTCH1 HD Domain Mutants / Endosomal Sorting Complex Required For Transport (ESCRT) / NOTCH2 Activation and Transmission of Signal to the Nucleus / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / cellular response to amino acid starvation / Downregulation of ERBB4 signaling / p75NTR recruits signalling complexes / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / APC-Cdc20 mediated degradation of Nek2A / PINK1-PRKN Mediated Mitophagy / TRAF6-mediated induction of TAK1 complex within TLR4 complex / InlA-mediated entry of Listeria monocytogenes into host cells / Pexophagy / Regulation of innate immune responses to cytosolic DNA / VLDLR internalisation and degradation / Downregulation of ERBB2:ERBB3 signaling / NRIF signals cell death from the nucleus / Activated NOTCH1 Transmits Signal to the Nucleus / Translesion synthesis by REV1 / NF-kB is activated and signals survival / Regulation of PTEN localization / Translesion synthesis by POLK / Regulation of BACH1 activity / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by POLI / Gap-filling DNA repair synthesis and ligation in GG-NER / MAP3K8 (TPL2)-dependent MAPK1/3 activation / TICAM1, RIP1-mediated IKK complex recruitment / Downregulation of TGF-beta receptor signaling / Josephin domain DUBs / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Regulation of activated PAK-2p34 by proteasome mediated degradation / InlB-mediated entry of Listeria monocytogenes into host cell / IKK complex recruitment mediated by RIP1 / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Autodegradation of Cdh1 by Cdh1:APC/C / TNFR1-induced NF-kappa-B signaling pathway / APC/C:Cdc20 mediated degradation of Securin / Asymmetric localization of PCP proteins / TCF dependent signaling in response to WNT / SCF-beta-TrCP mediated degradation of Emi1 / Regulation of NF-kappa B signaling / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / AUF1 (hnRNP D0) binds and destabilizes mRNA / Negative regulators of DDX58/IFIH1 signaling / TNFR2 non-canonical NF-kB pathway / NOTCH3 Activation and Transmission of Signal to the Nucleus / activated TAK1 mediates p38 MAPK activation / Assembly of the pre-replicative complex / Vpu mediated degradation of CD4 / Deactivation of the beta-catenin transactivating complex / Degradation of DVL / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Recognition of DNA damage by PCNA-containing replication complex / Regulation of signaling by CBL / Dectin-1 mediated noncanonical NF-kB signaling / Hh mutants are degraded by ERAD / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / nucleotide-excision repair / mitochondrial membrane / Fanconi Anemia Pathway / Negative regulation of FGFR3 signaling / Termination of translesion DNA synthesis
Similarity search - Function
Cathepsin B; Chain A - #40 / Unstructured region C-term to UIM in Ataxin3 / Machado-Joseph disease protein / Josephin domain / Josephin / Josephin domain profile. / Josephin / Ubiquitin interaction motif / S15/NS1, RNA-binding / Ubiquitin-interacting motif. ...Cathepsin B; Chain A - #40 / Unstructured region C-term to UIM in Ataxin3 / Machado-Joseph disease protein / Josephin domain / Josephin / Josephin domain profile. / Josephin / Ubiquitin interaction motif / S15/NS1, RNA-binding / Ubiquitin-interacting motif. / Ubiquitin interacting motif / Ubiquitin-interacting motif (UIM) domain profile. / Cathepsin B; Chain A / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 1 / Ubiquitin conserved site / Ubiquitin domain / Ubiquitin domain signature. / Ubiquitin-like (UB roll) / Ubiquitin family / Ubiquitin homologues / Ubiquitin-like domain / Ubiquitin domain profile. / Helix Hairpins / Ubiquitin-like domain superfamily / Roll / Alpha-Beta Complex / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Polyubiquitin-C / Ataxin-3 / UBC protein
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodSOLUTION NMR / torsion angle dynamics
Model detailstrascription/protein binding, machado-joseph disease protein, ubiquitin-proteasome pathway
AuthorsNicastro, G. / Masino, L. / Esposito, V. / Menon, R. / Pastore, A.
Citation
Journal: To be Published
Title: Understanding the plasticity of the ubiquitin-protein recognition code: the josephin domain of ataxin-3 is a diubiquitin binding motif
Authors: Nicastro, G. / Menon, R. / Masino, L. / Pastore, A.
#1: Journal: Proc.Natl.Acad.Sci.USA / Year: 2005
Title: The solution structure of the Josephin domain of ataxin-3: structural determinants for molecular recognition.
Authors: Nicastro, G. / Masino, L. / Esposito, V. / Menon, R. / Pastore, A.
History
DepositionJun 27, 2007Deposition site: BMRB / Processing site: RCSB
Revision 1.0Jul 1, 2008Provider: repository / Type: Initial release
Revision 1.1Jul 13, 2011Group: Version format compliance
Revision 1.2Mar 9, 2022Group: Data collection / Database references / Derived calculations
Category: database_2 / pdbx_nmr_spectrometer ...database_2 / pdbx_nmr_spectrometer / pdbx_struct_assembly / pdbx_struct_oper_list
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_nmr_spectrometer.model

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Ataxin-3
B: UBC protein
C: UBC protein


Theoretical massNumber of molelcules
Total (without water)38,2073
Polymers38,2073
Non-polymers00
Water0
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)20 / 100structures with the lowest energy
RepresentativeModel #1lowest energy

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Components

#1: Protein Ataxin-3 / Ataxin 3 / Machado-Joseph disease protein 1 / Spinocerebellar ataxia type 3 protein


Mass: 21053.768 Da / Num. of mol.: 1
Fragment: N-terminal domain of ataxin-3 sequence database residues 1-182
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ATXN3, ATX3, MJD, MJD1, SCA3 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 / Variant (production host): DE3
References: UniProt: P54252, Hydrolases; Acting on peptide bonds (peptidases); Cysteine endopeptidases
#2: Protein UBC protein


Mass: 8576.831 Da / Num. of mol.: 2 / Fragment: sequence database residues 318-469
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: UBC / Production host: Escherichia coli (E. coli) / Strain (production host): BL21 / Variant (production host): DE3 / References: UniProt: Q96H31, UniProt: P0CG48*PLUS

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Experimental details

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Experiment

ExperimentMethod: SOLUTION NMR
Details: trascription/protein binding, machado-joseph disease protein, ubiquitin-proteasome pathway
NMR experiment
Conditions-IDExperiment-IDSolution-IDType
1112D 1H-15N HSQC
1212D 1H-13C HSQC
1313D 1H-15N NOESY-HSQC
1413D 1H-13C NOESY-HSQC
1513D filtered 13C 15N

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Sample preparation

DetailsContents: 0.1 - 0.3 mM [U-15N] protein, 0.1 -0.3 mM [U-13C; U-15N] protein, 0.1-0.3 mM protein, 0.1-0.3 mM [U-13C; U-15N; U-2H] protein, 90% H2O/10% D2O
Solvent system: 90% H2O/10% D2O
Sample
Conc. (mg/ml)ComponentIsotopic labelingSolution-ID
0.1 mMentity-1[U-15N]1
0.1 mMentity-2[U-13C; U-15N]1
0.1 mMentity-31
0.1 mMentity-4[U-13C; U-15N; U-2H]1
Sample conditionsIonic strength: 0.01 / pH: 6.5 / Pressure: ambient / Temperature: 298 K

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NMR measurement

NMR spectrometer
TypeManufacturerModelField strength (MHz)Spectrometer-ID
Varian INOVAVarianINOVA8001
Varian INOVAVarianINOVA6002
Bruker AvanceBrukerAVANCE6003

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Processing

NMR software
NameVersionDeveloperClassification
ARIA2.1Linge, O'Donoghue and Nilgesstructure solution
HADDOCK2Dominguez, Boelens, Bonvinstructure solution
HADDOCK2Dominguez, Boelens, Bonvinrefinement
RefinementMethod: torsion angle dynamics / Software ordinal: 1 / Details: refinement in explicit solvent
NMR representativeSelection criteria: lowest energy
NMR ensembleConformer selection criteria: structures with the lowest energy
Conformers calculated total number: 100 / Conformers submitted total number: 20

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