[English] 日本語
Yorodumi
- EMDB-25744: Heptameric Human Twinkle Helicase Clinical Variant W315L -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-25744
TitleHeptameric Human Twinkle Helicase Clinical Variant W315L
Map data
Sample
  • Complex: Heptameric Human Twinkle Clinical Variant W315L
    • Protein or peptide: Twinkle mtDNA helicase
KeywordsHelicase / walker A / walker B / DNA binding / DNA BINDING PROTEIN
Function / homology
Function and homology information


mitochondrial chromosome / Strand-asynchronous mitochondrial DNA replication / mitochondrial DNA replication / mitochondrial transcription / DNA 5'-3' helicase / protein hexamerization / mitochondrial nucleoid / Mitochondrial protein degradation / DNA helicase activity / Transcriptional activation of mitochondrial biogenesis ...mitochondrial chromosome / Strand-asynchronous mitochondrial DNA replication / mitochondrial DNA replication / mitochondrial transcription / DNA 5'-3' helicase / protein hexamerization / mitochondrial nucleoid / Mitochondrial protein degradation / DNA helicase activity / Transcriptional activation of mitochondrial biogenesis / DNA-templated DNA replication / single-stranded DNA binding / protease binding / 5'-3' DNA helicase activity / mitochondrial inner membrane / mitochondrial matrix / lipid binding / ATP hydrolysis activity / mitochondrion / ATP binding / identical protein binding
Similarity search - Function
AAA domain / Twinkle-like protein / Archaeal primase DnaG/twinkle-like, TOPRIM domain / DNA helicase, DnaB-like, C-terminal / Superfamily 4 helicase domain profile. / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Twinkle mtDNA helicase
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 4.5 Å
AuthorsRiccio AA / Bouvette J
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of Environmental Health Sciences (NIH/NIEHS)Z01 ES065078 United States
National Institutes of Health/National Institute of Environmental Health Sciences (NIH/NIEHS)Z01 ES065080 United States
CitationJournal: Proc Natl Acad Sci U S A / Year: 2022
Title: Structural insight and characterization of human Twinkle helicase in mitochondrial disease.
Authors: Amanda A Riccio / Jonathan Bouvette / Lalith Perera / Matthew J Longley / Juno M Krahn / Jason G Williams / Robert Dutcher / Mario J Borgnia / William C Copeland /
Abstract: Twinkle is the mammalian helicase vital for replication and integrity of mitochondrial DNA. Over 90 Twinkle helicase disease variants have been linked to progressive external ophthalmoplegia and ...Twinkle is the mammalian helicase vital for replication and integrity of mitochondrial DNA. Over 90 Twinkle helicase disease variants have been linked to progressive external ophthalmoplegia and ataxia neuropathies among other mitochondrial diseases. Despite the biological and clinical importance, Twinkle represents the only remaining component of the human minimal mitochondrial replisome that has yet to be structurally characterized. Here, we present 3-dimensional structures of human Twinkle W315L. Employing cryo-electron microscopy (cryo-EM), we characterize the oligomeric assemblies of human full-length Twinkle W315L, define its multimeric interface, and map clinical variants associated with Twinkle in inherited mitochondrial disease. Cryo-EM, crosslinking-mass spectrometry, and molecular dynamics simulations provide insight into the dynamic movement and molecular consequences of the W315L clinical variant. Collectively, this ensemble of structures outlines a framework for studying Twinkle function in mitochondrial DNA replication and associated disease states.
History
DepositionDec 16, 2021-
Header (metadata) releaseJul 27, 2022-
Map releaseJul 27, 2022-
UpdateMay 21, 2025-
Current statusMay 21, 2025Processing site: RCSB / Status: Released

-
Structure visualization

Supplemental images

emd_25744.png

Downloads & links

-
Map

FileDownload / File: emd_25744.map.gz / Format: CCP4 / Size: 244.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.06 Å/pix.
x 400 pix.
= 423.2 Å		1.06 Å/pix.
x 400 pix.
= 423.2 Å		1.06 Å/pix.
x 400 pix.
= 423.2 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 1.058 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.159
Minimum - Maximum-0.0018964667 - 1.9148407
Average (Standard dev.)0.0010859101 (±0.023866678)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions400400400
Spacing400400400
CellA=B=C: 423.19998 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Mask #1

Fileemd_25744_msk_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_25744_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #1

Fileemd_25744_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Heptameric Human Twinkle Clinical Variant W315L

EntireName: Heptameric Human Twinkle Clinical Variant W315L
Components
  • Complex: Heptameric Human Twinkle Clinical Variant W315L
    • Protein or peptide: Twinkle mtDNA helicase

-
Supramolecule #1: Heptameric Human Twinkle Clinical Variant W315L

SupramoleculeName: Heptameric Human Twinkle Clinical Variant W315L / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 504 KDa

-
Macromolecule #1: Twinkle mtDNA helicase

MacromoleculeName: Twinkle mtDNA helicase / type: protein_or_peptide / ID: 1 / Number of copies: 7 / Enantiomer: LEVO / EC number: DNA helicase
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 78.469422 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MWVLLRSGYP LRILLPLRGE WMGRRGLPRN LAPGPPRRRY RKETLQALDM PVLPVTATEI RQYLRGHGIP FQDGHSCLRA LSPFAESSQ LKGQTGVTTS FSLFIDKTTG HFLCMTSLAE GSWEDFQASV EGRGDGAREG FLLSKAPEFE DSEEVRRIWN R AIPLWELP ...String:
MWVLLRSGYP LRILLPLRGE WMGRRGLPRN LAPGPPRRRY RKETLQALDM PVLPVTATEI RQYLRGHGIP FQDGHSCLRA LSPFAESSQ LKGQTGVTTS FSLFIDKTTG HFLCMTSLAE GSWEDFQASV EGRGDGAREG FLLSKAPEFE DSEEVRRIWN R AIPLWELP DQEEVQLADT MFGLTKVTDD TLKRFSVRYL RPARSLVFPW FSPGGSGLRG LKLLEAKCQG DGVSYEETTI PR PSAYHNL FGLPLISRRD AEVVLTSREL DSLALNQSTG LPTLTLPRGT TCLPPALLPY LEQFRRIVFW LGDDLRSLEA AKL FARKLN PKRCFLVRPG DQQPRPLEAL NGGFNLSRIL RTALPAWHKS IVSFRQLREE VLGELSNVEQ AAGLRWSRFP DLNR ILKGH RKGELTVFTG PTGSGKTTFI SEYALDLCSQ GVNTLWGSFE ISNVRLARVM LTQFAEGRLE DQLDKYDHWA DRFED LPLY FMTFHGQQSI RTVIDTMQHA VYVYDICHVI IDNLQFMMGH EQLSTDRIAA QDYIIGVFRK FATDNNCHVT LVIHPR KED DDKELQTASI FGSAKASQEA DNVLILQDRK LVTGPGKRYL QVSKNRFDGD VGVFPLEFNK NSLTFSIPPK NKARLKK IK DDTGPVAKKP SSGKKGATTQ NSEICSGQAP TPDQPDTSKR SKAAALEHHH HHH

UniProtKB: Twinkle mtDNA helicase

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

Concentration1.2 mg/mL
BufferpH: 8
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 60.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

+
Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: OTHER
Final reconstructionApplied symmetry - Point group: C7 (7 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 4.5 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 55655
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

+
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