[English] 日本語
Yorodumi
- EMDB-17214: Human Mitochondrial Lon Y186E Mutant ADP Bound -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: EMDB / ID: EMD-17214
TitleHuman Mitochondrial Lon Y186E Mutant ADP Bound
Map data
Sample
  • Complex: Human mitochondrial Lon protease
    • Protein or peptide: Lon protease homolog, mitochondrial
KeywordsHuman mitochondrial AAA+ protease / motor protein / HYDROLASE
Function / homology
Function and homology information


oxidation-dependent protein catabolic process / PH domain binding / mitochondrial protein catabolic process / G-quadruplex DNA binding / endopeptidase La / mitochondrial DNA metabolic process / mitochondrial genome maintenance / ATP-dependent peptidase activity / protein quality control for misfolded or incompletely synthesized proteins / mitochondrial nucleoid ...oxidation-dependent protein catabolic process / PH domain binding / mitochondrial protein catabolic process / G-quadruplex DNA binding / endopeptidase La / mitochondrial DNA metabolic process / mitochondrial genome maintenance / ATP-dependent peptidase activity / protein quality control for misfolded or incompletely synthesized proteins / mitochondrial nucleoid / insulin receptor substrate binding / chaperone-mediated protein complex assembly / DNA polymerase binding / regulation of peptidyl-tyrosine phosphorylation / negative regulation of insulin receptor signaling pathway / Mitochondrial protein degradation / proteolysis involved in protein catabolic process / mitochondrion organization / ADP binding / protein catabolic process / single-stranded DNA binding / cellular response to oxidative stress / sequence-specific DNA binding / single-stranded RNA binding / response to hypoxia / mitochondrial matrix / serine-type endopeptidase activity / ATP hydrolysis activity / mitochondrion / nucleoplasm / ATP binding / identical protein binding / membrane / cytosol
Similarity search - Function
Lon protease homologue, chloroplastic/mitochondrial / Lon protease, bacterial/eukaryotic-type / Lon protease AAA+ ATPase lid domain / Peptidase S16, active site / ATP-dependent serine proteases, lon family, serine active site. / Lon proteolytic domain profile. / Peptidase S16, Lon proteolytic domain / Lon protease / Lon protease (S16) C-terminal proteolytic domain / Lon N-terminal domain profile. ...Lon protease homologue, chloroplastic/mitochondrial / Lon protease, bacterial/eukaryotic-type / Lon protease AAA+ ATPase lid domain / Peptidase S16, active site / ATP-dependent serine proteases, lon family, serine active site. / Lon proteolytic domain profile. / Peptidase S16, Lon proteolytic domain / Lon protease / Lon protease (S16) C-terminal proteolytic domain / Lon N-terminal domain profile. / Lon protease, N-terminal domain / Lon protease, N-terminal domain superfamily / ATP-dependent protease La (LON) substrate-binding domain / Found in ATP-dependent protease La (LON) / PUA-like superfamily / ATPase family associated with various cellular activities (AAA) / ATPase, AAA-type, core / Ribosomal protein S5 domain 2-type fold, subgroup / Ribosomal protein S5 domain 2-type fold / ATPases associated with a variety of cellular activities / AAA+ ATPase domain / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Lon protease homolog, mitochondrial
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 8.47 Å
AuthorsKereiche S / Bauer JA / Matyas P / Novacek J / Kutejova E
Funding supportEuropean Union, Czech Republic, 7 items
OrganizationGrant numberCountry
Other governmentAPVV-15-0375
Other governmentAPVV-19-0298
Other governmentVEGA-2/0069/23
Other governmentVEGA-2/0131/20
European Regional Development FundITMS:305011X666European Union
Ministry of Education, Youth and Sports of the Czech RepublicCIISB project LM2018127 Czech Republic
Czech Science Foundation1825144Y Czech Republic
CitationJournal: Sci Rep / Year: 2024
Title: Polyphosphate and tyrosine phosphorylation in the N-terminal domain of the human mitochondrial Lon protease disrupts its functions.
Authors: Nina Kunová / Gabriela Ondrovičová / Jacob A Bauer / Veronika Krajčovičová / Matyáš Pinkas / Barbora Stojkovičová / Henrieta Havalová / Veronika Lukáčová / Lenka Kohútová / ...Authors: Nina Kunová / Gabriela Ondrovičová / Jacob A Bauer / Veronika Krajčovičová / Matyáš Pinkas / Barbora Stojkovičová / Henrieta Havalová / Veronika Lukáčová / Lenka Kohútová / Július Košťan / Lucia Martináková / Peter Baráth / Jiří Nováček / Sebastian Zoll / Sami Kereϊche / Eva Kutejová / Vladimír Pevala /
Abstract: Phosphorylation plays a crucial role in the regulation of many fundamental cellular processes. Phosphorylation levels are increased in many cancer cells where they may promote changes in ...Phosphorylation plays a crucial role in the regulation of many fundamental cellular processes. Phosphorylation levels are increased in many cancer cells where they may promote changes in mitochondrial homeostasis. Proteomic studies on various types of cancer identified 17 phosphorylation sites within the human ATP-dependent protease Lon, which degrades misfolded, unassembled and oxidatively damaged proteins in mitochondria. Most of these sites were found in Lon's N-terminal (NTD) and ATPase domains, though little is known about the effects on their function. By combining the biochemical and cryo-electron microscopy studies, we show the effect of Tyr186 and Tyr394 phosphorylations in Lon's NTD, which greatly reduce all Lon activities without affecting its ability to bind substrates or perturbing its tertiary structure. A substantial reduction in Lon's activities is also observed in the presence of polyphosphate, whose amount significantly increases in cancer cells. Our study thus provides an insight into the possible fine-tuning of Lon activities in human diseases, which highlights Lon's importance in maintaining proteostasis in mitochondria.
History
DepositionApr 26, 2023-
Header (metadata) releaseMay 8, 2024-
Map releaseMay 8, 2024-
UpdateNov 13, 2024-
Current statusNov 13, 2024Processing site: PDBe / Status: Released

-
Structure visualization

Supplemental images

emd_17214.png

Downloads & links

-
Map

FileDownload / File: emd_17214.map.gz / Format: CCP4 / Size: 35.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
2.44 Å/pix.
x 210 pix.
= 512.4 Å		2.44 Å/pix.
x 210 pix.
= 512.4 Å		2.44 Å/pix.
x 210 pix.
= 512.4 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 2.44 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 1.684
Minimum - Maximum-2.9172926 - 4.5086045
Average (Standard dev.)-0.0071433736 (±0.20980445)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions210210210
Spacing210210210
CellA=B=C: 512.4 Å
α=β=γ: 90.0 °

-
Supplemental data

-
Half map: #1

Fileemd_17214_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Half map: #2

Fileemd_17214_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

-
Sample components

-
Entire : Human mitochondrial Lon protease

EntireName: Human mitochondrial Lon protease
Components
  • Complex: Human mitochondrial Lon protease
    • Protein or peptide: Lon protease homolog, mitochondrial

-
Supramolecule #1: Human mitochondrial Lon protease

SupramoleculeName: Human mitochondrial Lon protease / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Homo sapiens (human) / Organelle: mitochondria

-
Macromolecule #1: Lon protease homolog, mitochondrial

MacromoleculeName: Lon protease homolog, mitochondrial / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO / EC number: endopeptidase La
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 98.241883 KDa
Recombinant expressionOrganism: Escherichia coli (E. coli)
SequenceString: MGHHHHHHDY DIPTTENLYF QGAHMTIPDV FPHLPLIAIT RNPVFPRFIK IIEVKNKKLV ELLRRKVRLA QPYVGVFLKR DDSNESDVV ESLDEI(1PA)HTG TFAQIHEMQD LGDKLRMIVM GHRRVHISRQ LEVEPEEPEA ENKHKPRRKS KRGKKEA ED ELSARHPAEL ...String:
MGHHHHHHDY DIPTTENLYF QGAHMTIPDV FPHLPLIAIT RNPVFPRFIK IIEVKNKKLV ELLRRKVRLA QPYVGVFLKR DDSNESDVV ESLDEI(1PA)HTG TFAQIHEMQD LGDKLRMIVM GHRRVHISRQ LEVEPEEPEA ENKHKPRRKS KRGKKEA ED ELSARHPAEL AMEPTPELPA EVLMVEVENV VHEDFQVTEE VKALTAEIVK TIRDIIALNP LYRESVLQMM QAGQRVVD N PIYLSDMGAA LTGAESHELQ DVLEETNIPK RLYKALSLLK KEFELSKLQQ RLGREVEEKI KQTHRKYLLQ EQLKIIKKE LGLEKDDKDA IEEKFRERLK ELVVPKHVMD VVDEELSKLG LLDNHSSEFN VTRNYLDWLT SIPWGKYSNE NLDLARAQAV LEEDHYGME DVKKRILEFI AVSQLRGSTQ GKILCFYGPP GVGKTSIARS IARALNREYF RFSVGGMTDV AEIKGHRRTY V GAMPGKII QCLKKTKTEN PLILIDEVDK IGRGYQGDPS SALLELLDPE QNANFLDHYL DVPVDLSKVL FICTANVTDT IP EPLRDRM EMINVSGYVA QEKLAIAERY LVPQARALCG LDESKAKLSS DVLTLLIKQY CRESGVRNLQ KQVEKVLRKS AYK IVSGEA ESVEVTPENL QDFVGKPVFT VERMYDVTPP GVVMGLAWTA MGGSTLFVET SLRRPQDKDA KGDKDGSLEV TGQL GEVMK ESARIAYTFA RAFLMQHAPA NDYLVTSHIH LHVPEGATPK DGPSAGCTIV TALLSLAMGR PVRQNLAMTG EVSLT GKIL PVGGIKEKTI AAKRAGVTCI VLPAENKKDF YDLAAFITEG LEVHFVEHYR EIFDIAFPDE QAEALAVER

UniProtKB: Lon protease homolog, mitochondrial

-
Experimental details

-
Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

-
Sample preparation

BufferpH: 7
VitrificationCryogen name: ETHANE

-
Electron microscopy

MicroscopeFEI TALOS ARCTICA
Image recordingFilm or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 0.5 µm
Experimental equipment
Model: Talos Arctica / Image courtesy: FEI Company

+
Image processing

Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 8.47 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 23915
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

-
Atomic model buiding 1

Initial modelPDB ID:

7nfy


Chain - Chain ID: A / Chain - Source name: PDB / Chain - Initial model type: experimental model
RefinementSpace: REAL / Protocol: FLEXIBLE FIT
Output model

PDB-8ovg:
Human Mitochondrial Lon Y186E Mutant ADP Bound

+
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