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Open data
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Basic information
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Title | Human Mitochondrial Lon Y186E Mutant ADP Bound | ||||||||||||||||||||||||
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![]() | Human mitochondrial AAA+ protease / ![]() ![]() | ||||||||||||||||||||||||
Function / homology | ![]() oxidation-dependent protein catabolic process / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||||||||||||||||||||
Biological species | ![]() ![]() | ||||||||||||||||||||||||
Method | ![]() ![]() | ||||||||||||||||||||||||
![]() | Kereiche S / Bauer JA / Matyas P / Novacek J / Kutejova E | ||||||||||||||||||||||||
Funding support | European Union, ![]()
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![]() | ![]() 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. | ||||||||||||||||||||||||
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 33.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16 KB 16 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 7.3 KB | Display | ![]() |
Images | ![]() | 106.3 KB | ||
Filedesc metadata | ![]() | 6.1 KB | ||
Others | ![]() ![]() | 32.8 MB 32.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8ovgMC ![]() 8ojlC ![]() 8okaC ![]() 8om7C ![]() 8ovfC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 2.44 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #1
File | emd_17214_half_map_1.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_17214_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Human mitochondrial Lon protease
Entire | Name: Human mitochondrial Lon protease |
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Components |
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-Supramolecule #1: Human mitochondrial Lon protease
Supramolecule | Name: Human mitochondrial Lon protease / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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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: ![]() |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 98.241883 KDa |
Recombinant expression | Organism: ![]() ![]() ![]() |
Sequence | String: 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
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Buffer | pH: 7 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TALOS ARCTICA |
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Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average electron dose: 40.0 e/Å2 |
Experimental equipment | ![]() Model: Talos Arctica / Image courtesy: FEI Company |