+
Open data
-
Basic information
Entry | ![]() | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Human Mitochondrial Lon Y394E Mutant ADP Bound | ||||||||||||||||||||||||
![]() | |||||||||||||||||||||||||
![]() |
| ||||||||||||||||||||||||
![]() | Human mitochondrial AAA+ protease / motor protein / HYDROLASE | ||||||||||||||||||||||||
Function / homology | ![]() 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 / regulation of peptidyl-tyrosine phosphorylation / insulin receptor substrate binding / chaperone-mediated protein complex assembly / DNA polymerase binding / negative regulation of insulin receptor signaling pathway / mitochondrion organization / proteolysis involved in protein catabolic process / Mitochondrial protein degradation / protein catabolic process / ADP binding / 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 | ||||||||||||||||||||||||
Biological species | ![]() | ||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.88 Å | ||||||||||||||||||||||||
![]() | Kereiche S / Bauer JA / Matyas P / Novacek J / Kutejova E | ||||||||||||||||||||||||
Funding support | European Union, ![]()
| ||||||||||||||||||||||||
![]() | ![]() 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 |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 114.4 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 16.4 KB 16.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.1 KB | Display | ![]() |
Images | ![]() | 139.7 KB | ||
Filedesc metadata | ![]() | 6.2 KB | ||
Others | ![]() ![]() | 115.7 MB 115.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8ojlMC ![]() 8okaC ![]() 8om7C ![]() 8ovfC ![]() 8ovgC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Voxel size | X=Y=Z: 1.227 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Half map: #2
File | emd_16915_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: #1
File | emd_16915_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : Human mitochondrial Lon protease
Entire | Name: Human mitochondrial Lon protease |
---|---|
Components |
|
-Supramolecule #1: Human mitochondrial Lon protease
Supramolecule | Name: Human mitochondrial Lon protease / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
---|---|
Source (natural) | Organism: ![]() |
-Macromolecule #1: Lon protease homolog, mitochondrial
Macromolecule | Name: Lon protease homolog, mitochondrial / type: protein_or_peptide / ID: 1 / Number of copies: 6 / Enantiomer: LEVO / EC number: endopeptidase La |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 98.165789 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MTIPDVMGHH HHHHDYDIPT TENLYFQGAH FPHLPLIAIT RNPVFPRFIK IIEVKNKKLV ELLRRKVRLA QPYVGVFLKR DDSNESDVV ESLDEIYHTG TFAQIHEMQD LGDKLRMIVM GHRRVHISRQ LEVEPEEPEA ENKHKPRRKS KRGKKEAEDE L SARHPAEL ...String: MTIPDVMGHH HHHHDYDIPT TENLYFQGAH FPHLPLIAIT RNPVFPRFIK IIEVKNKKLV ELLRRKVRLA QPYVGVFLKR DDSNESDVV ESLDEIYHTG TFAQIHEMQD LGDKLRMIVM GHRRVHISRQ LEVEPEEPEA ENKHKPRRKS KRGKKEAEDE L SARHPAEL AMEPTPELPA EVLMVEVENV VHEDFQVTEE VKALTAEIVK TIRDIIALNP LYRESVLQMM QAGQRVVDNP IY LSDMGAA LTGAESHELQ DVLEETNIPK RLYKALSLLK KEFELSKLQQ RLGREVEEKI KQTHRKELLQ EQLKIIKKEL GLE KDDKDA IEEKFRERLK ELVVPKHVMD VVDEELSKLG LLDNHSSEFN VTRNYLDWLT SIPWGKYSNE NLDLARAQAV LEED HYGME DVKKRILEFI AVSQLRGSTQ GKILCFYGPP GVGKTSIARS IARALNREYF RFSVGGMTDV AEIKGHRRTY VGAMP GKII QCLKKTKTEN PLILIDEVDK IGRGYQGDPS SALLELLDPE QNANFLDHYL DVPVDLSKVL FICTANVTDT IPEPLR DRM EMINVSGYVA QEKLAIAERY LVPQARALCG LDESKAKLSS DVLTLLIKQY CRESGVRNLQ KQVEKVLRKS AYKIVSG EA ESVEVTPENL QDFVGKPVFT VERMYDVTPP GVVMGLAWTA MGGSTLFVET SLRRPQDKDA KGDKDGSLEV TGQLGEVM K ESARIAYTFA RAFLMQHAPA NDYLVTSHIH LHVPEGATPK DGPSAGCTIV TALLSLAMGR PVRQNLAMTG EVSLTGKIL PVGGIKEKTI AAKRAGVTCI VLPAENKKDF YDLAAFITEG LEVHFVEHYR EIFDIAFPDE QAEALAVER UniProtKB: Lon protease homolog, mitochondrial |
-Macromolecule #2: ADENOSINE-5'-DIPHOSPHATE
Macromolecule | Name: ADENOSINE-5'-DIPHOSPHATE / type: ligand / ID: 2 / Number of copies: 6 / Formula: ADP |
---|---|
Molecular weight | Theoretical: 427.201 Da |
Chemical component information | ![]() ChemComp-ADP: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Buffer | pH: 7 |
---|---|
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 40.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |