[English] 日本語
Yorodumi
- EMDB-45601: Human E3 ligase E6AP in complex with HPV16-E6 and p53 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-45601
TitleHuman E3 ligase E6AP in complex with HPV16-E6 and p53
Map data
Sample
  • Complex: Ternary complex of E6AP with viral factor E6 and neosubstrate p53
    • Protein or peptide: Ubiquitin-protein ligase E3A
    • Protein or peptide: Immunoglobulin G-binding protein G/Cellular tumor antigen p53 fusion protein
    • Protein or peptide: Protein E6
KeywordsComplex / Viral / Ubiquitination / LIGASE
Function / homology
Function and homology information


sperm entry / positive regulation of Golgi lumen acidification / symbiont-mediated suppression of host transcription / regulation of ubiquitin-dependent protein catabolic process / symbiont-mediated suppression of host apoptosis / prostate gland growth / HECT-type E3 ubiquitin transferase / negative regulation of helicase activity / Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression ...sperm entry / positive regulation of Golgi lumen acidification / symbiont-mediated suppression of host transcription / regulation of ubiquitin-dependent protein catabolic process / symbiont-mediated suppression of host apoptosis / prostate gland growth / HECT-type E3 ubiquitin transferase / negative regulation of helicase activity / Loss of function of TP53 in cancer due to loss of tetramerization ability / Regulation of TP53 Expression / signal transduction by p53 class mediator / negative regulation of G1 to G0 transition / negative regulation of glucose catabolic process to lactate via pyruvate / Transcriptional activation of cell cycle inhibitor p21 / regulation of intrinsic apoptotic signaling pathway by p53 class mediator / negative regulation of pentose-phosphate shunt / ATP-dependent DNA/DNA annealing activity / Activation of NOXA and translocation to mitochondria / regulation of cell cycle G2/M phase transition / oligodendrocyte apoptotic process / negative regulation of miRNA processing / intrinsic apoptotic signaling pathway in response to hypoxia / regulation of fibroblast apoptotic process / positive regulation of thymocyte apoptotic process / oxidative stress-induced premature senescence / regulation of tissue remodeling / positive regulation of mitochondrial membrane permeability / mRNA transcription / bone marrow development / circadian behavior / positive regulation of programmed necrotic cell death / T cell proliferation involved in immune response / regulation of Cdc42 protein signal transduction / regulation of mitochondrial membrane permeability involved in apoptotic process / histone deacetylase regulator activity / RUNX3 regulates CDKN1A transcription / germ cell nucleus / homolactic fermentation / TP53 Regulates Transcription of Death Receptors and Ligands / TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain / Activation of PUMA and translocation to mitochondria / IgG binding / Regulation of TP53 Activity through Association with Co-factors / regulation of DNA damage response, signal transduction by p53 class mediator / negative regulation of glial cell proliferation / negative regulation of neuroblast proliferation / mitochondrial DNA repair / T cell lineage commitment / Formation of Senescence-Associated Heterochromatin Foci (SAHF) / thymocyte apoptotic process / ER overload response / TP53 Regulates Transcription of Caspase Activators and Caspases / cardiac septum morphogenesis / B cell lineage commitment / entrainment of circadian clock by photoperiod / androgen receptor signaling pathway / negative regulation of mitophagy / negative regulation of DNA replication / Zygotic genome activation (ZGA) / Association of TriC/CCT with target proteins during biosynthesis / PI5P Regulates TP53 Acetylation / TP53 Regulates Transcription of Genes Involved in Cytochrome C Release / necroptotic process / positive regulation of release of cytochrome c from mitochondria / negative regulation of telomere maintenance via telomerase / SUMOylation of transcription factors / TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain / TFIID-class transcription factor complex binding / cellular response to actinomycin D / intrinsic apoptotic signaling pathway by p53 class mediator / negative regulation of reactive oxygen species metabolic process / rRNA transcription / Transcriptional Regulation by VENTX / cellular response to UV-C / viral process / regulation of proteolysis / replicative senescence / general transcription initiation factor binding / progesterone receptor signaling pathway / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / positive regulation of RNA polymerase II transcription preinitiation complex assembly / neuroblast proliferation / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / Pyroptosis / positive regulation of execution phase of apoptosis / embryonic organ development / hematopoietic stem cell differentiation / response to X-ray / chromosome organization / type II interferon-mediated signaling pathway / TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest / somitogenesis / postsynaptic cytosol / hematopoietic progenitor cell differentiation / positive regulation of cardiac muscle cell apoptotic process / core promoter sequence-specific DNA binding / glial cell proliferation / negative regulation of stem cell proliferation / ovarian follicle development / protein autoubiquitination
Similarity search - Function
Ubiquitin-protein ligase E3A / Ubiquitin-protein ligase E3A, N-terminal zinc-binding domain / Ubiquitin-protein ligase E3A, N-terminal zinc-binding domain superfamily / Amino-terminal Zinc-binding domain of ubiquitin ligase E3A / Ubiquitin-protein ligase E3B/C / E6 early regulatory protein / E6 superfamily / Early Protein (E6) / IgG-binding B / B domain ...Ubiquitin-protein ligase E3A / Ubiquitin-protein ligase E3A, N-terminal zinc-binding domain / Ubiquitin-protein ligase E3A, N-terminal zinc-binding domain superfamily / Amino-terminal Zinc-binding domain of ubiquitin ligase E3A / Ubiquitin-protein ligase E3B/C / E6 early regulatory protein / E6 superfamily / Early Protein (E6) / IgG-binding B / B domain / M protein-type anchor domain / GA-like domain / GA-like domain / HECT domain / HECT, E3 ligase catalytic domain / HECT-domain (ubiquitin-transferase) / HECT domain profile. / Domain Homologous to E6-AP Carboxyl Terminus with / Immunoglobulin/albumin-binding domain superfamily / Cellular tumor antigen p53, transactivation domain 2 / Transactivation domain 2 / : / p53 transactivation domain / P53 transactivation motif / p53 family signature. / p53, tetramerisation domain / P53 tetramerisation motif / p53, DNA-binding domain / P53 DNA-binding domain / p53 tumour suppressor family / p53-like tetramerisation domain superfamily / p53/RUNT-type transcription factor, DNA-binding domain superfamily / YSIRK Gram-positive signal peptide / LPXTG cell wall anchor motif / Gram-positive cocci surface proteins LPxTG motif profile. / LPXTG cell wall anchor domain / p53-like transcription factor, DNA-binding
Similarity search - Domain/homology
Protein E6 / Cellular tumor antigen p53 / Immunoglobulin G-binding protein G / Ubiquitin-protein ligase E3A
Similarity search - Component
Biological speciesHomo sapiens (human) / Human papillomavirus 16
Methodsingle particle reconstruction / cryo EM / Resolution: 3.54 Å
AuthorsKenny S / Das C
Funding support United States, 3 items
OrganizationGrant numberCountry
Other privateP30CA023168
American Heart Association905924/SK/2021 United States
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)T32 GM132024 United States
CitationJournal: Structure / Year: 2025
Title: Structure of E6AP in complex with HPV16-E6 and p53 reveals a novel ordered domain important for E3 ligase activation.
Authors: Sebastian Kenny / Shalini Iyer / Clinton A Gabel / Natalia Tegenfeldt / Andrew G DeMarco / Mark C Hall / Leifu Chang / V Jo Davisson / Scott Vande Pol / Chittaranjan Das /
Abstract: High-risk human papillomavirus E6 oncoprotein is a model system for the recognition and degradation of cellular p53 tumor suppressor protein. There remains a gap in the understanding of the ubiquitin ...High-risk human papillomavirus E6 oncoprotein is a model system for the recognition and degradation of cellular p53 tumor suppressor protein. There remains a gap in the understanding of the ubiquitin transfer reaction, including placement of the E6AP catalytic HECT domain of the ligase concerning the p53 substrate and how E6 itself is protected from ubiquitination. We determined the cryoelectron microscopy (cryo-EM) structure of the E6AP/E6/p53 complex, related the structure to in vivo modeling of the tri-molecular complex, and identified structural interactions associated with activation of the ubiquitin ligase function. The structure reveals that the N-terminal ordered domain (NOD) in E6AP has a terminal alpha helix that mediates the interaction of the NOD with the HECT domain of E6AP and protects the HPV-E6 protein from ubiquitination. In addition, this NOD helix is required for E6AP ligase function by contributing to the affinity of the E6-E6AP association, modulating E6 substrate recognition, while displacing UbcH7.
History
DepositionJul 2, 2024-
Header (metadata) releaseJan 8, 2025-
Map releaseJan 8, 2025-
UpdateMar 19, 2025-
Current statusMar 19, 2025Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_45601.png

Downloads & links

-
Map

FileDownload / File: emd_45601.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.86 Å/pix.
x 256 pix.
= 220.16 Å		0.86 Å/pix.
x 256 pix.
= 220.16 Å		0.86 Å/pix.
x 256 pix.
= 220.16 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.86 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.316
Minimum - Maximum-3.2597888 - 5.208333
Average (Standard dev.)0.0016058313 (±0.088757455)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions256256256
Spacing256256256
CellA=B=C: 220.16 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #2

Fileemd_45601_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_45601_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Ternary complex of E6AP with viral factor E6 and neosubstrate p53

EntireName: Ternary complex of E6AP with viral factor E6 and neosubstrate p53
Components
  • Complex: Ternary complex of E6AP with viral factor E6 and neosubstrate p53
    • Protein or peptide: Ubiquitin-protein ligase E3A
    • Protein or peptide: Immunoglobulin G-binding protein G/Cellular tumor antigen p53 fusion protein
    • Protein or peptide: Protein E6

-
Supramolecule #1: Ternary complex of E6AP with viral factor E6 and neosubstrate p53

SupramoleculeName: Ternary complex of E6AP with viral factor E6 and neosubstrate p53
type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)

-
Macromolecule #1: Ubiquitin-protein ligase E3A

MacromoleculeName: Ubiquitin-protein ligase E3A / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: HECT-type E3 ubiquitin transferase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 102.982867 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString: MGSSHHHHHH SSGLVPRGSH MEKLHQCYWK SGEPQSDDIE ASRMKRAAAK HLIERYYHQL TEGCGNEACT NEFCASCPTF LRMDNNAAA IKALELYKIN AKLCDPHPSK KGASSAYLEN SKGAPNNSCS EIKMNKKGAR IDFKDVTYLT EEKVYEILEL C REREDYSP ...String:
MGSSHHHHHH SSGLVPRGSH MEKLHQCYWK SGEPQSDDIE ASRMKRAAAK HLIERYYHQL TEGCGNEACT NEFCASCPTF LRMDNNAAA IKALELYKIN AKLCDPHPSK KGASSAYLEN SKGAPNNSCS EIKMNKKGAR IDFKDVTYLT EEKVYEILEL C REREDYSP LIRVIGRVFS SAEALVQSFR KVKQHTKEEL KSLQAKDEDK DEDEKEKAAC SAAAMEEDSE ASSSRIGDSS QG DNNLQKL GPDDVSVDID AIRRVYTRLL SNEKIETAFL NALVYLSPNV ECDLTYHNVY SRDPNYLNLF IIVMENRNLH SPE YLEMAL PLFCKAMSKL PLAAQGKLIR LWSKYNADQI RRMMETFQQL ITYKVISNEF NSRNLVNDDD AIVAASKCLK MVYY ANVVG GEVDTNHNEE DDEEPIPESS ELTLQELLGE ERRNKKGPRV DPLETELGVK TLDCRKPLIP FEEFINEPLN EVLEM DKDY TFFKVETENK FSFMTCPFIL NAVTKNLGLY YDNRIRMYSE RRITVLYSLV QGQQLNPYLR LKVRRDHIID DALVRL EMI AMENPADLKK QLYVEFEGEQ GVDEGGVSKE FFQLVVEEIF NPDIGMFTYD ESTKLFWFNP SSFETEGQFT LIGIVLG LA IYNNCILDVH FPMVVYRKLM GKKGTFRDLG DSHPVLYQSL KDLLEYEGNV EDDMMITFQI SQTDLFGNPM MYDLKENG D KIPITNENRK EFVNLYSDYI LNKSVEKQFK AFRRGFHMVT NESPLKYLFR PEEIELLICG SRNLDFQALE ETTEYDGGY TRDSVLIREF WEIVHSFTDE QKRLFLQFTT GTDRAPVGGL GKLKMIIAKN GPDTERLPTS HTCFNVLLLP EYSSKEKLKE RLLKAITYA KGFGML

UniProtKB: Ubiquitin-protein ligase E3A

-
Macromolecule #2: Immunoglobulin G-binding protein G/Cellular tumor antigen p53 fus...

MacromoleculeName: Immunoglobulin G-binding protein G/Cellular tumor antigen p53 fusion protein
type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 43.801734 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString: MGHHHHHHSS GMTYKLILNG KTLKGETTTE AVDAATAEKV FKQYANDNGV DGEWTYDDAT KTFTVTEEFS SGSSGENLYF QGSHMEEPQ SDPSVEPPLS QETFSDLWKL LPENNVLSPL PSQAMDDLML SPDDIEQWFT EDPGPDEAPR MPEAAPPVAP A PAAPTPAA ...String:
MGHHHHHHSS GMTYKLILNG KTLKGETTTE AVDAATAEKV FKQYANDNGV DGEWTYDDAT KTFTVTEEFS SGSSGENLYF QGSHMEEPQ SDPSVEPPLS QETFSDLWKL LPENNVLSPL PSQAMDDLML SPDDIEQWFT EDPGPDEAPR MPEAAPPVAP A PAAPTPAA PAPAPSWPLS SSVPSQKTYQ GSYGFRLGFL HSGTAKSVTC TYSPALNKLF CQLAKTCPVQ LWVDSTPPPG TR VRAMAIY KQSQHMTEVV RRCPHHERCS DSDGLAPPQH LIRVEGNLRA EYLDDRNTFR HSVVVPYEPP EVGSDCTTIH YNY MCYSSC MGGMNRRPIL TIITLEDSSG NLLGRDSFEV RVCACPGRDR RTEEENLRKK GEPHHELPPG STKRALPNNT

UniProtKB: Immunoglobulin G-binding protein G, Cellular tumor antigen p53

-
Macromolecule #3: Protein E6

MacromoleculeName: Protein E6 / type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Human papillomavirus 16
Molecular weightTheoretical: 18.365369 KDa
Recombinant expressionOrganism: Escherichia coli BL21(DE3) (bacteria)
SequenceString:
MFQDPQERPR KLPQLCTELQ TTIHDIILEC VYCKQQLLRR EVYDFAFRDL CIVYRDGNPY AVCDKCLKFY SKISEYRHYC YSLYGTTLE QQYNKPLCDL LIRCINCQKP LCPEEKQRHL DKKQRFHNIR GRWTGRCMSC CRSSRTRRET QL

UniProtKB: Protein E6

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration0.25 mg/mL
BufferpH: 7.4
GridModel: Quantifoil R1.2/1.3
VitrificationCryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 279 K
Detailsmonodisperse, further purified by SEC

-
Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Number grids imaged: 1 / Number real images: 5548 / Average exposure time: 3.192 sec. / Average electron dose: 1.52 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.6 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

Particle selectionNumber selected: 1591147
Startup modelType of model: INSILICO MODEL / In silico model: AlphaFold2 model for E6AP and p53
Final reconstructionNumber classes used: 1 / Resolution.type: BY AUTHOR / Resolution: 3.54 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 3.2.0) / Number images used: 238679
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.2.0)
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: cryoSPARC (ver. 3.2.0)
Final 3D classificationNumber classes: 3 / Software - Name: cryoSPARC (ver. 3.2.0)

-
Atomic model buiding 1

Initial modelChain - Source name: AlphaFold / Chain - Initial model type: in silico model
RefinementSpace: REAL / Protocol: RIGID BODY FIT / Target criteria: Cross-correlation coefficient
Output model

PDB-9cht:
Human E3 ligase E6AP in complex with HPV16-E6 and p53

+
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