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- PDB-2lr1: Structural Mechanism for Bax Inhibition by Cytomegalovirus Protei... -

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Basic information

Entry
Database: PDB / ID: 2lr1
TitleStructural Mechanism for Bax Inhibition by Cytomegalovirus Protein vMIA
Components
  • Apoptosis regulator BAX
  • Immediate early glycoprotein
KeywordsAPOPTOSIS/SIGNALING PROTEIN / APOPTOSIS-SIGNALING PROTEIN complex
Function / homology
Function and homology information


: / T cell homeostatic proliferation / release of matrix enzymes from mitochondria / positive regulation of developmental pigmentation / protein insertion into mitochondrial membrane / BAX complex / B cell receptor apoptotic signaling pathway / positive regulation of reproductive process / positive regulation of motor neuron apoptotic process / regulation of mammary gland epithelial cell proliferation ...: / T cell homeostatic proliferation / release of matrix enzymes from mitochondria / positive regulation of developmental pigmentation / protein insertion into mitochondrial membrane / BAX complex / B cell receptor apoptotic signaling pathway / positive regulation of reproductive process / positive regulation of motor neuron apoptotic process / regulation of mammary gland epithelial cell proliferation / spermatid differentiation / Activation, translocation and oligomerization of BAX / positive regulation of B cell apoptotic process / development of secondary sexual characteristics / NTRK3 as a dependence receptor / Sertoli cell proliferation / positive regulation of apoptotic DNA fragmentation / B cell homeostatic proliferation / glycosphingolipid metabolic process / positive regulation of mitochondrial membrane permeability involved in apoptotic process / retinal cell programmed cell death / B cell negative selection / BAK complex / apoptotic process involved in blood vessel morphogenesis / mitochondrial fragmentation involved in apoptotic process / negative regulation of endoplasmic reticulum calcium ion concentration / regulation of mitochondrial membrane permeability involved in programmed necrotic cell death / apoptotic process involved in embryonic digit morphogenesis / Release of apoptotic factors from the mitochondria / mitochondrial permeability transition pore complex / post-embryonic camera-type eye morphogenesis / establishment or maintenance of transmembrane electrochemical gradient / apoptotic process involved in mammary gland involution / Transcriptional regulation by RUNX2 / positive regulation of apoptotic process involved in mammary gland involution / regulation of nitrogen utilization / B cell apoptotic process / positive regulation of endoplasmic reticulum unfolded protein response / endoplasmic reticulum calcium ion homeostasis / fertilization / positive regulation of epithelial cell apoptotic process / calcium ion transport into cytosol / motor neuron apoptotic process / channel activity / mitochondrial fusion / Bcl-2 family protein complex / epithelial cell apoptotic process / myeloid cell homeostasis / BH domain binding / execution phase of apoptosis / hypothalamus development / host cell mitochondrial membrane / positive regulation of calcium ion transport into cytosol / thymocyte apoptotic process / pore complex / odontogenesis of dentin-containing tooth / negative regulation of peptidyl-serine phosphorylation / BH3 domain binding / germ cell development / positive regulation of IRE1-mediated unfolded protein response / host cell Golgi membrane / positive regulation of release of cytochrome c from mitochondria / apoptotic mitochondrial changes / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / vagina development / B cell homeostasis / negative regulation of mitochondrial membrane potential / negative regulation of apoptotic signaling pathway / intrinsic apoptotic signaling pathway by p53 class mediator / extrinsic apoptotic signaling pathway via death domain receptors / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / response to axon injury / blood vessel remodeling / ectopic germ cell programmed cell death / cellular response to unfolded protein / Pyroptosis / supramolecular fiber organization / negative regulation of fibroblast proliferation / extrinsic apoptotic signaling pathway / positive regulation of intrinsic apoptotic signaling pathway / ovarian follicle development / release of sequestered calcium ion into cytosol / extrinsic apoptotic signaling pathway in absence of ligand / homeostasis of number of cells within a tissue / response to salt stress / Hsp70 protein binding / intrinsic apoptotic signaling pathway / positive regulation of release of sequestered calcium ion into cytosol / TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest / release of cytochrome c from mitochondria / regulation of mitochondrial membrane potential / negative regulation of protein binding / kidney development / response to gamma radiation / apoptotic signaling pathway / neuron migration / positive regulation of protein-containing complex assembly / response to toxic substance / cellular response to virus / cerebral cortex development
Similarity search - Function
Herpesvirus UL37, HHV-5-related / Betaherpesvirus immediate-early glycoprotein UL37 / Blc2-like / Apoptosis Regulator Bcl-x / Apoptosis regulator, Bcl-2, BH3 motif, conserved site / Apoptosis regulator, Bcl-2 family BH3 motif signature. / Apoptosis regulator, Bcl-2, BH1 motif, conserved site / Apoptosis regulator, Bcl-2 family BH1 motif signature. / Apoptosis regulator, Bcl-2, BH2 motif, conserved site / Apoptosis regulator, Bcl-2 family BH2 motif signature. ...Herpesvirus UL37, HHV-5-related / Betaherpesvirus immediate-early glycoprotein UL37 / Blc2-like / Apoptosis Regulator Bcl-x / Apoptosis regulator, Bcl-2, BH3 motif, conserved site / Apoptosis regulator, Bcl-2 family BH3 motif signature. / Apoptosis regulator, Bcl-2, BH1 motif, conserved site / Apoptosis regulator, Bcl-2 family BH1 motif signature. / Apoptosis regulator, Bcl-2, BH2 motif, conserved site / Apoptosis regulator, Bcl-2 family BH2 motif signature. / BCL (B-Cell lymphoma); contains BH1, BH2 regions / Bcl-2 family / Bcl-2, Bcl-2 homology region 1-3 / Bcl2-like / Apoptosis regulator proteins, Bcl-2 family / BCL2-like apoptosis inhibitors family profile. / Bcl-2-like superfamily / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
UL37 immediate early glycoprotein / Apoptosis regulator BAX
Similarity search - Component
Biological speciesHomo sapiens (human)
Human herpesvirus 5
MethodSOLUTION NMR / DGSA-distance geometry simulated annealing
Model detailslowest energy, model 1
AuthorsMa, J.
CitationJournal: Proc.Natl.Acad.Sci.USA / Year: 2012
Title: Structural mechanism of Bax inhibition by cytomegalovirus protein vMIA.
Authors: Ma, J. / Edlich, F. / Bermejo, G.A. / Norris, K.L. / Youle, R.J. / Tjandra, N.
History
DepositionMar 20, 2012Deposition site: BMRB / Processing site: RCSB
Revision 1.0Dec 5, 2012Provider: repository / Type: Initial release
Revision 1.1Jan 16, 2013Group: Database references
Revision 1.2Feb 22, 2017Group: Other
Revision 1.3May 1, 2024Group: Data collection / Database references
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_nmr_spectrometer
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: Apoptosis regulator BAX
B: Immediate early glycoprotein


Theoretical massNumber of molelcules
Total (without water)23,9372
Polymers23,9372
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
NMR ensembles
DataCriteria
Number of conformers (submitted / calculated)20 / 500structures with the lowest energy
RepresentativeModel #1lowest energy

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Components

#1: Protein Apoptosis regulator BAX / Bcl-2-like protein 4 / Bcl2-L-4


Mass: 21204.355 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: BAX, BCL2L4 / Production host: Escherichia coli (E. coli) / References: UniProt: Q07812
#2: Protein/peptide Immediate early glycoprotein


Mass: 2732.289 Da / Num. of mol.: 1 / Fragment: UNP residues 130-150 / Source method: obtained synthetically / Details: strain AD169 / Source: (synth.) Human herpesvirus 5 / References: UniProt: P16778

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Experimental details

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Experiment

ExperimentMethod: SOLUTION NMR
NMR experiment
Conditions-IDExperiment-IDSolution-IDType
1122D 1H-15N HSQC
1212D 1H-1H TOCSY
1312D 1H-1H NOESY
1413D HNCO
1513D HN(CA)CB
1612D 1H-15N HSQC
1713D 1H-15N NOESY
1812D 1H-13C HSQC
1913D 1H-13C NOESY
11012D DQF-COSY

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Sample preparation

Details
Solution-IDContentsSolvent system
10.1 mM protein_1, 0.1 mM [U-100% 13C; U-100% 15N] protein_2, 20 mM potassium phosphate, 5 M [U-100% 2H] D2O, 50 M H2O, DTT, 90% H2O/10% D2O90% H2O/10% D2O
20.1 mM [U-100% 15N] protein_1, 0.1 mM protein_2, 20 mM potassium phosphate, 5 M [U-100% 2H] D2O, 50 M H2O, DTT, 90% H2O/10% D2O90% H2O/10% D2O
Sample
Conc. (mg/ml)ComponentIsotopic labelingSolution-ID
0.1 mMentity_1-11
0.1 mMentity_2-2[U-100% 13C; U-100% 15N]1
20 mMpotassium phosphate-31
5 MD2O-4[U-100% 2H]1
50 MH2O-51
0.1 mMentity_1-7[U-100% 15N]2
0.1 mMentity_2-82
20 mMpotassium phosphate-92
5 MD2O-10[U-100% 2H]2
50 MH2O-112
Sample conditionsIonic strength: 50 / pH: 6.2 / Pressure: ambient / Temperature: 310 K

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NMR measurement

NMR spectrometerType: Bruker Avance / Manufacturer: Bruker / Model: AVANCE / Field strength: 800 MHz

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Processing

NMR software
NameDeveloperClassification
xplorSchwieters, Kuszewski, Tjandra and Clorestructure solution
xplorSchwieters, Kuszewski, Tjandra and Clorerefinement
RefinementMethod: DGSA-distance geometry simulated annealing / Software ordinal: 1
NMR representativeSelection criteria: lowest energy
NMR ensembleConformer selection criteria: structures with the lowest energy
Conformers calculated total number: 500 / Conformers submitted total number: 20

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