[English] 日本語
Yorodumi
- PDB-6bvb: Crystal structure of HIF-2alpha-pVHL-elongin B-elongin C -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6bvb
TitleCrystal structure of HIF-2alpha-pVHL-elongin B-elongin C
Components
  • Elongin-B
  • Elongin-C
  • Hypoxia-Inducible Factor 2 alpha
  • von Hippel-Lindau disease tumor suppressor
KeywordsGENE REGULATION / E3 Ubiquitin Ligase
Function / homology
Function and homology information


myoblast fate commitment / Cellular response to hypoxia / regulation of protein neddylation / Transcriptional regulation of pluripotent stem cells / PTK6 Expression / regulation of cellular response to hypoxia / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / transcription elongation factor activity / norepinephrine metabolic process ...myoblast fate commitment / Cellular response to hypoxia / regulation of protein neddylation / Transcriptional regulation of pluripotent stem cells / PTK6 Expression / regulation of cellular response to hypoxia / RHOBTB3 ATPase cycle / negative regulation of receptor signaling pathway via JAK-STAT / transcription elongation factor activity / norepinephrine metabolic process / target-directed miRNA degradation / elongin complex / VCB complex / surfactant homeostasis / epithelial cell maturation / Replication of the SARS-CoV-1 genome / Cul5-RING ubiquitin ligase complex / Regulation of gene expression by Hypoxia-inducible Factor / Cul2-RING ubiquitin ligase complex / intracellular non-membrane-bounded organelle / SUMOylation of ubiquitinylation proteins / negative regulation of transcription elongation by RNA polymerase II / Pausing and recovery of Tat-mediated HIV elongation / Tat-mediated HIV elongation arrest and recovery / HIV elongation arrest and recovery / Pausing and recovery of HIV elongation / ubiquitin-like ligase-substrate adaptor activity / embryonic placenta development / Tat-mediated elongation of the HIV-1 transcript / blood vessel remodeling / Formation of HIV-1 elongation complex containing HIV-1 Tat / Formation of HIV elongation complex in the absence of HIV Tat / negative regulation of signal transduction / RNA Polymerase II Transcription Elongation / Formation of RNA Pol II elongation complex / negative regulation of TORC1 signaling / RNA Polymerase II Pre-transcription Events / visual perception / Pexophagy / regulation of heart rate / negative regulation of autophagy / mitochondrion organization / erythrocyte differentiation / transcription corepressor binding / transcription elongation by RNA polymerase II / positive regulation of cell differentiation / TP53 Regulates Transcription of DNA Repair Genes / transcription initiation at RNA polymerase II promoter / RNA polymerase II transcription regulatory region sequence-specific DNA binding / Vif-mediated degradation of APOBEC3G / lung development / mRNA transcription by RNA polymerase II / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / cell morphogenesis / Inactivation of CSF3 (G-CSF) signaling / Evasion by RSV of host interferon responses / Regulation of expression of SLITs and ROBOs / transcription coactivator binding / multicellular organismal-level iron ion homeostasis / ubiquitin-protein transferase activity / transcription corepressor activity / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / protein-macromolecule adaptor activity / Neddylation / positive regulation of cold-induced thermogenesis / Replication of the SARS-CoV-2 genome / cellular response to hypoxia / ubiquitin-dependent protein catabolic process / regulation of gene expression / protein-containing complex assembly / DNA-binding transcription activator activity, RNA polymerase II-specific / proteasome-mediated ubiquitin-dependent protein catabolic process / angiogenesis / DNA-binding transcription factor binding / RNA polymerase II-specific DNA-binding transcription factor binding / response to oxidative stress / amyloid fibril formation / transcription regulator complex / molecular adaptor activity / protein stabilization / response to hypoxia / DNA-binding transcription factor activity, RNA polymerase II-specific / protein ubiquitination / nuclear speck / protein heterodimerization activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of cell population proliferation / negative regulation of gene expression / ubiquitin protein ligase binding / regulation of DNA-templated transcription / chromatin / regulation of transcription by RNA polymerase II / negative regulation of apoptotic process / positive regulation of DNA-templated transcription / enzyme binding / negative regulation of transcription by RNA polymerase II / endoplasmic reticulum / signal transduction / positive regulation of transcription by RNA polymerase II
Similarity search - Function
von Hippel-Lindau disease tumour suppressor, alpha domain / von Hippel-Lindau disease tumour suppressor, beta domain / Elongin C; Chain C, domain 1 / HIF-1 alpha, transactivation domain, C-terminal / HIF-1 alpha C terminal transactivation domain / Hypoxia-inducible factor, alpha subunit-like / Hypoxia-inducible factor-1 / Nuclear translocator / von Hippel-Lindau disease tumour suppressor, beta/alpha domain / von Hippel-Lindau disease tumour suppressor, alpha domain ...von Hippel-Lindau disease tumour suppressor, alpha domain / von Hippel-Lindau disease tumour suppressor, beta domain / Elongin C; Chain C, domain 1 / HIF-1 alpha, transactivation domain, C-terminal / HIF-1 alpha C terminal transactivation domain / Hypoxia-inducible factor, alpha subunit-like / Hypoxia-inducible factor-1 / Nuclear translocator / von Hippel-Lindau disease tumour suppressor, beta/alpha domain / von Hippel-Lindau disease tumour suppressor, alpha domain / von Hippel-Lindau disease tumour suppressor, beta domain / VHL superfamily / von Hippel-Lindau disease tumour suppressor, alpha domain superfamily / von Hippel-Lindau disease tumour suppressor, beta domain superfamily / VHL beta domain / VHL box domain / Elongin B / Elongin-C / Potassium Channel Kv1.1; Chain A / Potassium Channel Kv1.1; Chain A / PAC motif / Motif C-terminal to PAS motifs (likely to contribute to PAS structural domain) / S-phase kinase-associated protein 1-like / SKP1 component, POZ domain / Skp1 family, tetramerisation domain / Found in Skp1 protein family / PAS domain / Helix-loop-helix DNA-binding domain superfamily / helix loop helix domain / Myc-type, basic helix-loop-helix (bHLH) domain / Myc-type, basic helix-loop-helix (bHLH) domain profile. / PAS fold / PAS fold / SKP1/BTB/POZ domain superfamily / Phosphatidylinositol 3-kinase Catalytic Subunit; Chain A, domain 1 / PAS domain / PAS repeat profile. / PAS domain / PAS domain superfamily / Ubiquitin-like (UB roll) / Ubiquitin family / Ubiquitin homologues / Ubiquitin domain profile. / Ubiquitin-like domain / Ubiquitin-like domain superfamily / Roll / Immunoglobulin-like / Sandwich / 2-Layer Sandwich / Orthogonal Bundle / Mainly Beta / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
von Hippel-Lindau disease tumor suppressor / Elongin-C / Elongin-B / Endothelial PAS domain-containing protein 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.002 Å
AuthorsTarade, D. / Ohh, M. / Lee, J.E.
Funding support Canada, 3items
OrganizationGrant numberCountry
Canadian Institutes of Health Research (CIHR)MOP-77718 (M.O) Canada
Canadian Institutes of Health Research (CIHR)MOP-136978 (M.O) Canada
Canadian Institutes of Health Research (CIHR)MOP-133694 (J.E.L) Canada
CitationJournal: Nat Commun / Year: 2018
Title: HIF-2 alpha-pVHL complex reveals broad genotype-phenotype correlations in HIF-2 alpha-driven disease.
Authors: Tarade, D. / Robinson, C.M. / Lee, J.E. / Ohh, M.
History
DepositionDec 12, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Aug 1, 2018Provider: repository / Type: Initial release
Revision 1.1Sep 5, 2018Group: Data collection / Database references / Source and taxonomy
Category: citation / entity_src_gen
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _entity_src_gen.pdbx_host_org_strain
Revision 1.2Jan 8, 2020Group: Author supporting evidence / Category: pdbx_audit_support
Item: _pdbx_audit_support.country / _pdbx_audit_support.funding_organization
Revision 1.3Oct 4, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
V: von Hippel-Lindau disease tumor suppressor
B: Elongin-B
C: Elongin-C
H: Hypoxia-Inducible Factor 2 alpha


Theoretical massNumber of molelcules
Total (without water)44,8914
Polymers44,8914
Non-polymers00
Water1,838102
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration, VHL-elongin B-elongin C (VBC) complex is supported by size exclusion chromatography. Biolayer interferometry kinetic binding experiments confirm binding of VBC complex to peptide substrate.
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area6110 Å2
ΔGint-47 kcal/mol
Surface area17640 Å2
MethodPISA
Unit cell
Length a, b, c (Å)59.770, 59.770, 246.100
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number96
Space group name H-MP43212

-
Components

#1: Protein von Hippel-Lindau disease tumor suppressor / Protein G7 / pVHL


Mass: 18702.291 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: VHL / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: P40337
#2: Protein Elongin-B / EloB / Elongin 18 kDa subunit / RNA polymerase II transcription factor SIII subunit B / SIII p18 / ...EloB / Elongin 18 kDa subunit / RNA polymerase II transcription factor SIII subunit B / SIII p18 / Transcription elongation factor B polypeptide 2


Mass: 13147.781 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ELOB, TCEB2 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: Q15370
#3: Protein Elongin-C / EloC / Elongin 15 kDa subunit / RNA polymerase II transcription factor SIII subunit C / SIII p15 / ...EloC / Elongin 15 kDa subunit / RNA polymerase II transcription factor SIII subunit C / SIII p15 / Transcription elongation factor B polypeptide 1


Mass: 10843.420 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ELOC, TCEB1 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3) / References: UniProt: Q15369
#4: Protein/peptide Hypoxia-Inducible Factor 2 alpha


Mass: 2197.416 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q99814*PLUS
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 102 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.45 Å3/Da / Density % sol: 49.76 % / Description: Trapezoidal plates.
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: 26% (v/v) PEG-3350, 0.2 M Li2SO4, 0.1 M Bis-Tris. 7 mg/mL protein complex.
Temp details: Drops were set at 277 K. Incubated at 293 K.

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: CLSI / Beamline: 08ID-1 / Wavelength: 1.28339 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Sep 10, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.28339 Å / Relative weight: 1
ReflectionResolution: 2.002→48.307 Å / Num. obs: 31053 / % possible obs: 99.3 % / Redundancy: 8.54 % / CC1/2: 0.997 / Rrim(I) all: 0.095 / Net I/σ(I): 13.2
Reflection shellResolution: 2.002→2.05 Å / Redundancy: 3.81 % / Mean I/σ(I) obs: 1.32 / Num. unique obs: 2084 / CC1/2: 0.701 / Rrim(I) all: 0.912 / % possible all: 92.2

-
Processing

Software
NameVersionClassification
PHENIX(1.12_2829)refinement
XDSdata reduction
XSCALEdata scaling
PHENIXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1LM8

1lm8


Resolution: 2.002→48.307 Å / SU ML: 0.24 / Cross valid method: FREE R-VALUE / σ(F): 1.36 / Phase error: 22.85
RfactorNum. reflection% reflection
Rfree0.2355 1553 5 %
Rwork0.1986 --
obs0.2005 31047 99.3 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Refinement stepCycle: LAST / Resolution: 2.002→48.307 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2790 0 0 102 2892
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0122861
X-RAY DIFFRACTIONf_angle_d1.0943900
X-RAY DIFFRACTIONf_dihedral_angle_d15.2711740
X-RAY DIFFRACTIONf_chiral_restr0.061451
X-RAY DIFFRACTIONf_plane_restr0.008505
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.002-2.06660.34091290.29862452X-RAY DIFFRACTION93
2.0666-2.14050.25931380.2742612X-RAY DIFFRACTION99
2.1405-2.22620.31731400.23342658X-RAY DIFFRACTION100
2.2262-2.32750.24081370.21872607X-RAY DIFFRACTION100
2.3275-2.45020.23041390.20622657X-RAY DIFFRACTION100
2.4502-2.60370.25731420.21082686X-RAY DIFFRACTION100
2.6037-2.80470.26961410.2162670X-RAY DIFFRACTION100
2.8047-3.08690.24321410.22382688X-RAY DIFFRACTION100
3.0869-3.53350.26181440.21172746X-RAY DIFFRACTION100
3.5335-4.45130.20511460.15892760X-RAY DIFFRACTION100
4.4513-48.32150.20691560.17832958X-RAY DIFFRACTION100
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
15.9293-1.47190.76627.1715-2.14456.43620.1005-0.22510.2325-0.3677-0.056-0.0288-0.18970.1846-0.09750.327-0.02270.05150.21610.03770.350445.261835.4697101.4883
24.7451-1.45492.32996.17590.61065.62230.26030.03280.2878-0.5152-0.1253-0.5433-0.1925-0.1209-0.08780.46350.01910.11540.23850.05750.372938.179342.300796.3569
34.98464.9377-1.30096.4817-4.74237.8391-0.02930.0593-0.7980.19150.4041.11740.2424-2.1822-0.50040.3114-0.03620.06890.62510.08920.599734.011430.2512108.3732
42.7646-1.1909-0.57611.08711.36132.27160.21380.31170.163-0.16-0.0460.05010.03810.0167-0.07270.3815-0.02910.00180.33170.00730.280248.392525.950196.4886
57.3566-1.9873-0.04584.27945.73229.05410.10790.08980.4637-0.1969-0.2369-0.1965-0.695-0.22510.08540.4054-0.06110.10630.2880.01950.404555.433736.1296104.4895
65.96222.61042.40646.44432.11753.5220.2447-0.06280.40380.1703-0.0015-0.2507-0.44890.3392-0.21360.3818-0.09440.00340.3634-0.07010.426460.038137.9958115.0659
72.4823-0.554-0.30052.44520.28053.50860.0364-0.16140.16980.04110.0784-0.17120.00490.2595-0.12830.2886-0.0598-0.00410.3167-0.0060.303152.066626.3474111.823
88.12442.80024.21259.60462.86536.9460.0365-0.1818-0.5149-0.46950.14161.2796-0.2047-0.43790.17260.45580.00470.10810.4860.08460.696825.124311.503139.2792
94.08220.3863-0.67431.69650.70764.011-0.0217-0.4041-0.27280.3528-0.04150.14920.369-0.35330.06520.4478-0.12570.02130.31360.04020.324635.959315.8134138.4821
106.3564-0.539-5.52273.17821.46067.75330.0121-0.25360.00460.31-0.10470.20030.0777-0.04880.05390.3789-0.14470.01440.3551-0.01820.340936.071419.5544136.3533
114.1469-2.2843-1.93132.48281.19614.36780.0229-0.2339-0.17320.1914-0.05740.03910.51520.4460.06890.4332-0.0526-0.05120.35610.0080.320150.472215.3931122.4778
123.43134.46222.63219.70810.10987.1459-0.65811.04020.7828-0.46280.96760.3052-0.22080.0614-0.40230.4001-0.0304-0.02750.62090.04970.461551.451223.1415140.2737
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1(chain B and resid 1:18)
2X-RAY DIFFRACTION2(chain B and resid 19:62)
3X-RAY DIFFRACTION3(chain B and resid 63:68)
4X-RAY DIFFRACTION4(chain B and resid 69:106)
5X-RAY DIFFRACTION5(chain C and resid 17:34)
6X-RAY DIFFRACTION6(chain C and resid 35:57)
7X-RAY DIFFRACTION7(chain C and resid 58:112)
8X-RAY DIFFRACTION8(chain H and resid 527:540)
9X-RAY DIFFRACTION9(chain V and resid 59:105)
10X-RAY DIFFRACTION10(chain V and resid 106:141)
11X-RAY DIFFRACTION11(chain V and resid 142:193)
12X-RAY DIFFRACTION12(chain V and resid 194:209)

+
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://pdbjlvh1.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