Proteopedia - User contributions [en]

Sandbox Reserved 1644

2021-01-13T19:14:51Z

Camille Spicher:

{{Sandbox_Reserved_ESBS20_}}
==2x36 - Structure of the proteolytic domain of the <scene name='86/868177/Structure_hmlon_protease/1'>Human Mitochondrial Lon protease</scene>==
<StructureSection load='2x36' size='340' side='right' caption='Structure of the Human Mitochondrial Lon protease' scene=''>

'''2x36''' is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This domain belongs to the [https://en.wikipedia.org/wiki/Lon_protease_family Lon protease family].
 
[https://en.wikipedia.org/wiki/Mitochondrion Mitochondrial] Lon [https://en.wikipedia.org/wiki/Protease protease] is an '''ATP-dependent serine protease''' involved in the selective degradation of abnormal proteins. [https://en.wikipedia.org/wiki/LONP1 LONP1] situated on chromosome 19 is the nuclear gene encoding mitochondrial Lon protein. The single species of [https://en.wikipedia.org/wiki/Messenger_RNA mRNA] of this protein is found in the mitochondrial matrix. This protein from human tissues has a molecular mass of 100 [https://en.wikipedia.org/wiki/Dalton_(unit) kDA].
 
== Function ==

The mitochondrial Lon protease is an important regulator of mitochondrial [https://en.wikipedia.org/wiki/Metabolism metabolism] including the maintenance and repair of mitochondrial [https://en.wikipedia.org/wiki/DNA DNA]. This protein is also essential for homeostasis of mitochondria, and by regulating some regulatory proteins which have a short life or damaged proteins.
 
Lon protease has three main roles.
This protein is able to do a '''[https://en.wikipedia.org/wiki/Proteolysis proteolytic] digestion''' of oxidized proteins which allows the renewal of essential mitochondrial enzymes such as [https://en.wikipedia.org/wiki/Aconitase aconitase] or [https://en.wikipedia.org/wiki/TFAM Mitochondrial transcription factor A].
Lon protease is involved in [https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] [https://en.wikipedia.org/wiki/DNA_replication replication] and [https://en.wikipedia.org/w/index.php?title=Mitogenesis&redirect=no mitogenesis] by being a '''mitochondrial [https://en.wikipedia.org/wiki/DNA-binding_protein DNA-bing protein]'''. Human Lon and mtDNA associate at the level of their at least 4 contiguous [https://en.wikipedia.org/wiki/Guanine guanine] sequence and form a [https://en.wikipedia.org/wiki/G-quadruplex G-quadruplex]<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>. This G-rich region is the control region for mtDNA replication and transcription<ref>Lu, Bin. “Mitochondrial Lon Protease and Cancer.” Advances in Experimental Medicine and Biology 1038 (2017): 173–82. https://doi.org/10.1007/978-981-10-6674-0_12.</ref>.
 
Mitochondrial Lon protease interacts with '''[https://en.wikipedia.org/wiki/Chaperone_(protein) protein chaperone]''', notably [https://en.wikipedia.org/wiki/Chaperonin HSP60]-[https://en.wikipedia.org/wiki/Hsp70 Hsp70] complex to protect cell from apoptosis under environmental stress<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>.
 
The mitochondrial Lon protease is essentially found in the cytoplasmic of mitochondria because [https://en.wikipedia.org/wiki/Amino_acid amino-acid] has a potential mitochondrial targetting presequences<ref>García-Nafría, Javier, Gabriela Ondrovičová, Elena Blagova, Vladimir M Levdikov, Jacob A Bauer, Carolyn K Suzuki, Eva Kutejová, Anthony J Wilkinson, and Keith S Wilson. “Structure of the Catalytic Domain of the Human Mitochondrial Lon Protease: Proposed Relation of Oligomer Formation and Activity.” Protein Science : A Publication of the Protein Society 19, no. 5 (May 2010): 987–99. https://doi.org/10.1002/pro.376.</ref>.
 
Lon Human protease alternates between cycles of '''being bound to the mitochondrial genome''' and '''being free into the mitochondrial cytoplasm''' where it can degrade abnormal proteins coming from damaged proteins, errors in the synthesis, or [https://en.wikipedia.org/wiki/Protein_folding misfolded] of multimeric proteins. Its inactive conformation prevents uncontrolled proteolysis.
To achieve proteolytic cleavage, the Lon protein has to form a hexamer.
Lon protease has also a role in mtDNA quality control by permits oxidative mitochondrial DNA damage. Sensitivities of H2O2-induced mtDNA damage depend on the proportion of LON<ref>Lu, Bin. “Mitochondrial Lon Protease and Cancer.” Advances in Experimental Medicine and Biology 1038 (2017): 173–82. https://doi.org/10.1007/978-981-10-6674-0_12.</ref>.
Other ATP-dependent proteases are found in eukaryotic cells and organelles like [https://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex 26S protease] which uses [https://en.wikipedia.org/wiki/ATP_hydrolysis ATP hydrolysis] for conjugation or ubiquitin for example.
 

== General structure ==

Lon proteins are grouped into two families, '''LonA''' and '''LonB'''. The human protein LonP1 is part of the LonA proteins <ref>« The N-terminal domain plays a crucial role in the structure of a full-length human mitochondrial Lon protease | Scientific Reports ». Consulté le 13 janvier 2021. https://www.nature.com/articles/srep33631.
</ref>. This protein has three isoforms obtained by [https://en.wikipedia.org/wiki/Alternative_splicing alternative splicing] of the portion of DNA coding for this protein <ref>He, Lihong, Dongyang Luo, Fan Yang, Chunhao Li, Xuegong Zhang, Haiteng Deng, et Jing-Ren Zhang. « Multiple domains of bacterial and human Lon proteases define substrate selectivity ». Emerging Microbes & Infections 7 (17 août 2018). https://doi.org/10.1038/s41426-018-0148-4.
</ref>.
Globally there is a great diversity of Lon proteins, but they are all organised in an oligomeric ring structure, mostly hexameric structure with identical subunits.
Lon proteins are therefore an hexameric chambered [https://en.wikipedia.org/wiki/Protease protease] complex. (This structure is similar with yeast [https://www.yeastgenome.org/locus/S000000118 Pim1] )
The six Lon monomers are forming three pairs of legs owned by the N-terminal domain of the protein. This structure is emerging of the protein as a trimer of dimers <ref>Kutejová, Eva. « Mitochondrial Lon protease-unique structure and essential function in mammalian cells ». Integrative Cancer Science and Therapeutics 5, nᵒ 6 (2018). https://doi.org/10.15761/ICST.1000296.
</ref>.
 
Like many proteins, Lon is a '''flexible''' peptide which has different '''three-dimensional conformations'''. The protein can therefore pass from one conformation to another by hydrolysis of [https://biologydictionary.net/atp/ ATP]<ref>Voos, Wolfgang, et Karen Pollecker. « The Mitochondrial Lon Protease: Novel Functions off the Beaten Track? » Biomolecules 10, nᵒ 2 (7 février 2020). https://doi.org/10.3390/biom10020253.
</ref>.
With these conformational changes, the [https://en.wikipedia.org/wiki/Active_site '''active sites'''] of the Lon protein are protected from the external environment in the oligomeric complex that forms the '''degradation chamber'''.
This form of degradation chamber is also found in bacteria, plants, fungi and metazoan, the similarities with bacteria are most probably due to the [https://en.wikipedia.org/wiki/Symbiogenesis endosymbiotic theory].
 
 
This protein has a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] and [https://en.wikipedia.org/wiki/Chaperone_(protein) '''chaperone''']-like activity, it cannot unfold aggregated proteins, but can participate in the assembling of some complexes). These two enzymatic activities are separated on two polypeptide chains forming a complex or two separate domains on the same polypeptide chain.
 
The Lon protein has three main distinct domains: the first, the '''N-terminal''' domain, is specialised in '''substrate binding''' and [https://en.wikipedia.org/wiki/Oligomer '''oligomerization''']. The second, called the '''AAA+ domain''' (or A domain) corresponds to the fixation and hydrolysis site of the [https://biologydictionary.net/atp/ATP ATP]. Finally, the third domain located at the '''C-terminal''' is an active serine site leading to '''substrate degradation'''. This is a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] domain, called domain P <ref>He, Lihong, Dongyang Luo, Fan Yang, Chunhao Li, Xuegong Zhang, Haiteng Deng, et Jing-Ren Zhang. « Multiple domains of bacterial and human Lon proteases define substrate selectivity ». Emerging Microbes & Infections 7 (17 août 2018). https://doi.org/10.1038/s41426-018-0148-4.
</ref>.
 
Mammalian Lon protein only interacts with '''single-stranded DNA''' (ssDNA) but not dsDNA. There are therefore special sequences for interaction with '''G-rich DNA''' as well as RNA. In addition, the binding of a substrate to the protein stimulates the interaction with the DNA.
[https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] binds to the Lon protein with different affinities depending on the state of the cell and the type of cell meeting the following four parameters <ref>Lu, Bin, Swati Yadav, Parul G. Shah, Tong Liu, Bin Tian, Sebastian Pukszta, Nerissa Villaluna, et al. « Roles for the Human ATP-Dependent Lon Protease in Mitochondrial DNA Maintenance ». Journal of Biological Chemistry 282, nᵒ 24 (15 juin 2007): 17363‑74. https://doi.org/10.1074/jbc.M611540200.
</ref>:
 
- the single stranding state of mtDNA
 
- the bioavailability of the mtDNA binding sites
 
- the affinity of the protein for a given DNA sequence
 
- the total number of high and low affinity Lon binding sites present

== Structural highlights ==

== Evolutionary conservation ==

== Disease ==

Various [https://en.wikipedia.org/wiki/Myopathy myopathy], [https://en.wikipedia.org/wiki/Type_2_diabetes type 2 diabetes], [https://en.wikipedia.org/wiki/Parkinson%27s_disease Parkinson's disease], or [https://en.wikipedia.org/wiki/Alzheimer%27s_disease Alzheimer's disease] are human [https://en.wikipedia.org/wiki/Degenerative_disease degenerative disease] partly due to abnormalities of the mitochondria<ref>Wang, N, S Gottesman, M C Willingham, M M Gottesman, and M R Maurizi. “A Human Mitochondrial ATP-Dependent Protease That Is Highly Homologous to Bacterial Lon Protease.” Proceedings of the National Academy of Sciences 90, no. 23 (December 1, 1993): 11247–51. https://doi.org/10.1073/pnas.90.23.11247.
</ref>. In fact, Lon protease has a role in [https://en.wikipedia.org/wiki/Cancer cancer], [https://en.wikipedia.org/wiki/Apoptosis apoptosis] and [https://en.wikipedia.org/wiki/Ageing aging] because this protein is an essential part of developmental pathways and stress response.
 
[https://en.wikipedia.org/wiki/Mutant Mutant] in Lon decreases the degradation capacity of proteins with abnormal conformations which lead to mitochondrial dysfunction. Mitochondrial dysfunction causes normal cells to become apoptotic, or to aberrant adaptation and selection of hypoxic phenotypes in pathological conditions like cancer<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>.
 
Lon expression is necessary for survival in mammals. Indeed, a [https://en.wikipedia.org/wiki/Zygosity#Homozygous homozygous] [https://en.wikipedia.org/wiki/Deletion_(genetics) deletion] of LONP1 is lethal for early embryonic<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mhttps://proteopedia.org/wiki/skins/common/images/button_extlink.pngitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>. Indeed, the [https://rarediseases.info.nih.gov/diseases/1418/codas-syndrome#:~:text=Summary,-Listen&text=Codas%20syndrome%20is%20a%20multiple,Dental%2C%20Auricular%20and%20Skeletal%20anomalies.&text=To%20date%2C%20three%20affected%20children,from%20Brazil)%20have%20been%20reported. CODAS Syndrome] is a rare and multi-system developmental disorder from heterozygous or homozygous mutations in LONP1 where all the affected children were very severely impacted by their disease.
 
The LONP1 gene is regulated, when the cell undergoes a heat shock, [https://en.wikipedia.org/wiki/Starvation starvation] or oxidative stress the gene is up-regulated. On the contrary, Lon is down-regulated with aging, extensive [https://en.wikipedia.org/wiki/Hypoxia hypoxia], and prolonged oxidative stress. So Lon is an important factor in aging and degenerative disease.
 
A [https://en.wikipedia.org/wiki/Consensus_sequence consensus] binding site of Nuclear Respiratory Factor 2 (NRF-2) is present on the region -623/+1 of the LONP1 promoter which is important for response to [https://en.wikipedia.org/wiki/Reactive_oxygen_species reactive oxygen species] related to oxidative stress. As well as the putative binding site in -2023/-1230 for [https://en.wikipedia.org/wiki/NF-%CE%BABhttps://en.wikipedia.org/wiki/NF-%CE%BAB NF-kB] in LONP1 which consolidate the role of Lon as a stress protein<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Lon Protease Preferentially Degrades Oxidized Mitochondrial Aconitase by an ATP-Stimulated Mechanism.” Nature Cell Biology 4, no. 9 (September 2002): 674–80. https://doi.org/10.1038/ncb836.</ref>.
 
Research is being done to use Lon as a therapeutic target for the treatment of cancer by developing novel Lon inhibitors.

 
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1644

2021-01-13T16:58:29Z

Camille Spicher:

{{Sandbox_Reserved_ESBS20_}}
==2x36 - Structure of the proteolytic domain of the Human Mitochondrial Lon protease==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

'''2x36''' is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This domain belongs to the [https://en.wikipedia.org/wiki/Lon_protease_family Lon protease family].
 
[https://en.wikipedia.org/wiki/Mitochondrion Mitochondrial] Lon [https://en.wikipedia.org/wiki/Protease protease] is an '''ATP-dependent serine protease''' involved in the selective degradation of abnormal proteins. [https://en.wikipedia.org/wiki/LONP1 LONP1] situated on chromosome 19 is the nuclear gene encoding mitochondrial Lon protein. The single species of [https://en.wikipedia.org/wiki/Messenger_RNA mRNA] of this protein is found in the mitochondrial matrix. This protein from human tissues has a molecular mass of 100 [https://en.wikipedia.org/wiki/Dalton_(unit) kDA].
 
== Function ==

The mitochondrial Lon protease is an important regulator of mitochondrial [https://en.wikipedia.org/wiki/Metabolism metabolism] including the maintenance and repair of mitochondrial [https://en.wikipedia.org/wiki/DNA DNA]. This protein is also essential for homeostasis of mitochondria, and by regulating some regulatory proteins which have a short life or damaged proteins.
 
Lon protease has three main roles.
This protein is able to do a '''[https://en.wikipedia.org/wiki/Proteolysis proteolytic] digestion''' of oxidized proteins which allows the renewal of essential mitochondrial enzymes such as [https://en.wikipedia.org/wiki/Aconitase aconitase] or [https://en.wikipedia.org/wiki/TFAM Mitochondrial transcription factor A].
Lon protease is involved in [https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] [https://en.wikipedia.org/wiki/DNA_replication replication] and [https://en.wikipedia.org/w/index.php?title=Mitogenesis&redirect=no mitogenesis] by being a '''mitochondrial [https://en.wikipedia.org/wiki/DNA-binding_protein DNA-bing protein]'''. Human Lon and mtDNA associate at the level of their at least 4 contiguous [https://en.wikipedia.org/wiki/Guanine guanine] sequence and form a [https://en.wikipedia.org/wiki/G-quadruplex G-quadruplex]<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>. This G-rich region is the control region for mtDNA replication and transcription<ref>Lu, Bin. “Mitochondrial Lon Protease and Cancer.” Advances in Experimental Medicine and Biology 1038 (2017): 173–82. https://doi.org/10.1007/978-981-10-6674-0_12.</ref>.
 
Mitochondrial Lon protease interacts with '''[https://en.wikipedia.org/wiki/Chaperone_(protein) protein chaperone]''', notably [https://en.wikipedia.org/wiki/Chaperonin HSP60]-[https://en.wikipedia.org/wiki/Hsp70 Hsp70] complex to protect cell from apoptosis under environmental stress<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>.
 
The mitochondrial Lon protease is essentially found in the cytoplasmic of mitochondria because [https://en.wikipedia.org/wiki/Amino_acid amino-acid] has a potential mitochondrial targetting presequences<ref>García-Nafría, Javier, Gabriela Ondrovičová, Elena Blagova, Vladimir M Levdikov, Jacob A Bauer, Carolyn K Suzuki, Eva Kutejová, Anthony J Wilkinson, and Keith S Wilson. “Structure of the Catalytic Domain of the Human Mitochondrial Lon Protease: Proposed Relation of Oligomer Formation and Activity.” Protein Science : A Publication of the Protein Society 19, no. 5 (May 2010): 987–99. https://doi.org/10.1002/pro.376.</ref>.
 
Lon Human protease alternates between cycles of '''being bound to the mitochondrial genome''' and '''being free into the mitochondrial cytoplasm''' where it can degrade abnormal proteins coming from damaged proteins, errors in the synthesis, or [https://en.wikipedia.org/wiki/Protein_folding misfolded] of multimeric proteins. Its inactive conformation prevents uncontrolled proteolysis.
To achieve proteolytic cleavage, the Lon protein has to form a hexamer.
Lon protease has also a role in mtDNA quality control by permits oxidative mitochondrial DNA damage. Sensitivities of H2O2-induced mtDNA damage depend on the proportion of LON<ref>Lu, Bin. “Mitochondrial Lon Protease and Cancer.” Advances in Experimental Medicine and Biology 1038 (2017): 173–82. https://doi.org/10.1007/978-981-10-6674-0_12.</ref>.
Other ATP-dependent proteases are found in eukaryotic cells and organelles like [https://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex 26S protease] which uses [https://en.wikipedia.org/wiki/ATP_hydrolysis ATP hydrolysis] for conjugation or ubiquitin for example.
 

== General structure ==

Lon proteins are grouped into two families, '''LonA''' and '''LonB'''. The human protein LonP1 is part of the LonA proteins <ref>« The N-terminal domain plays a crucial role in the structure of a full-length human mitochondrial Lon protease | Scientific Reports ». Consulté le 13 janvier 2021. https://www.nature.com/articles/srep33631.
</ref>. This protein has three isoforms obtained by [https://en.wikipedia.org/wiki/Alternative_splicing alternative splicing] of the portion of DNA coding for this protein <ref>He, Lihong, Dongyang Luo, Fan Yang, Chunhao Li, Xuegong Zhang, Haiteng Deng, et Jing-Ren Zhang. « Multiple domains of bacterial and human Lon proteases define substrate selectivity ». Emerging Microbes & Infections 7 (17 août 2018). https://doi.org/10.1038/s41426-018-0148-4.
</ref>.
Globally there is a great diversity of Lon proteins, but they are all organised in an oligomeric ring structure, mostly hexameric structure with identical subunits.
Lon proteins are therefore an hexameric chambered [https://en.wikipedia.org/wiki/Protease protease] complex. (This structure is similar with yeast [https://www.yeastgenome.org/locus/S000000118 Pim1] )
The six Lon monomers are forming three pairs of legs owned by the N-terminal domain of the protein. This structure is emerging of the protein as a trimer of dimers <ref>Kutejová, Eva. « Mitochondrial Lon protease-unique structure and essential function in mammalian cells ». Integrative Cancer Science and Therapeutics 5, nᵒ 6 (2018). https://doi.org/10.15761/ICST.1000296.
</ref>.
 
Like many proteins, Lon is a '''flexible''' peptide which has different '''three-dimensional conformations'''. The protein can therefore pass from one conformation to another by hydrolysis of [https://biologydictionary.net/atp/ ATP]<ref>Voos, Wolfgang, et Karen Pollecker. « The Mitochondrial Lon Protease: Novel Functions off the Beaten Track? » Biomolecules 10, nᵒ 2 (7 février 2020). https://doi.org/10.3390/biom10020253.
</ref>.
With these conformational changes, the [https://en.wikipedia.org/wiki/Active_site '''active sites'''] of the Lon protein are protected from the external environment in the oligomeric complex that forms the '''degradation chamber'''.
This form of degradation chamber is also found in bacteria, plants, fungi and metazoan, the similarities with bacteria are most probably due to the [https://en.wikipedia.org/wiki/Symbiogenesis endosymbiotic theory].
 
 
This protein has a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] and [https://en.wikipedia.org/wiki/Chaperone_(protein) '''chaperone''']-like activity, it cannot unfold aggregated proteins, but can participate in the assembling of some complexes). These two enzymatic activities are separated on two polypeptide chains forming a complex or two separate domains on the same polypeptide chain.
 
The Lon protein has three main distinct domains: the first, the '''N-terminal''' domain, is specialised in '''substrate binding''' and [https://en.wikipedia.org/wiki/Oligomer '''oligomerization''']. The second, called the '''AAA+ domain''' (or A domain) corresponds to the fixation and hydrolysis site of the [https://biologydictionary.net/atp/ATP ATP]. Finally, the third domain located at the '''C-terminal''' is an active serine site leading to '''substrate degradation'''. This is a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] domain, called domain P <ref>He, Lihong, Dongyang Luo, Fan Yang, Chunhao Li, Xuegong Zhang, Haiteng Deng, et Jing-Ren Zhang. « Multiple domains of bacterial and human Lon proteases define substrate selectivity ». Emerging Microbes & Infections 7 (17 août 2018). https://doi.org/10.1038/s41426-018-0148-4.
</ref>.
 
Mammalian Lon protein only interacts with '''single-stranded DNA''' (ssDNA) but not dsDNA. There are therefore special sequences for interaction with '''G-rich DNA''' as well as RNA. In addition, the binding of a substrate to the protein stimulates the interaction with the DNA.
[https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] binds to the Lon protein with different affinities depending on the state of the cell and the type of cell meeting the following four parameters <ref>Lu, Bin, Swati Yadav, Parul G. Shah, Tong Liu, Bin Tian, Sebastian Pukszta, Nerissa Villaluna, et al. « Roles for the Human ATP-Dependent Lon Protease in Mitochondrial DNA Maintenance ». Journal of Biological Chemistry 282, nᵒ 24 (15 juin 2007): 17363‑74. https://doi.org/10.1074/jbc.M611540200.
</ref>:
 
- the single stranding state of mtDNA
 
- the bioavailability of the mtDNA binding sites
 
- the affinity of the protein for a given DNA sequence
 
- the total number of high and low affinity Lon binding sites present

== Structural highlights ==

== Evolutionary conservation ==

== Disease ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1644

2021-01-13T16:55:44Z

Camille Spicher:

{{Sandbox_Reserved_ESBS20_}}
==2x36 - Structure of the proteolytic domain of the Human Mitochondrial Lon protease==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

'''2x36''' is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This domain belongs to the [https://en.wikipedia.org/wiki/Lon_protease_family Lon protease family].
 
[https://en.wikipedia.org/wiki/Mitochondrion Mitochondrial] Lon [https://en.wikipedia.org/wiki/Protease protease] is an '''ATP-dependent serine protease''' involved in the selective degradation of abnormal proteins. [https://en.wikipedia.org/wiki/LONP1 LONP1] situated on chromosome 19 is the nuclear gene encoding mitochondrial Lon protein. The single species of [https://en.wikipedia.org/wiki/Messenger_RNA mRNA] of this protein is found in the mitochondrial matrix. This protein from human tissues has a molecular mass of 100 [https://en.wikipedia.org/wiki/Dalton_(unit) kDA].
 
== Function ==

The mitochondrial Lon protease is an important regulator of mitochondrial [https://en.wikipedia.org/wiki/Metabolism metabolism] including the maintenance and repair of mitochondrial [https://en.wikipedia.org/wiki/DNA DNA]. This protein is also essential for homeostasis of mitochondria, and by regulating some regulatory proteins which have a short life or damaged proteins.
 
Lon protease has three main roles.
This protein is able to do a '''[https://en.wikipedia.org/wiki/Proteolysis proteolytic] digestion''' of oxidized proteins which allows the renewal of essential mitochondrial enzymes such as [https://en.wikipedia.org/wiki/Aconitase aconitase] or [https://en.wikipedia.org/wiki/TFAM Mitochondrial transcription factor A].
Lon protease is involved in [https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] [https://en.wikipedia.org/wiki/DNA_replication replication] and [https://en.wikipedia.org/w/index.php?title=Mitogenesis&redirect=no mitogenesis] by being a '''mitochondrial [https://en.wikipedia.org/wiki/DNA-binding_protein DNA-bing protein]'''. Human Lon and mtDNA associate at the level of their at least 4 contiguous [https://en.wikipedia.org/wiki/Guanine guanine] sequence and form a [https://en.wikipedia.org/wiki/G-quadruplex G-quadruplex]<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>. This G-rich region is the control region for mtDNA replication and transcription<ref>Lu, Bin. “Mitochondrial Lon Protease and Cancer.” Advances in Experimental Medicine and Biology 1038 (2017): 173–82. https://doi.org/10.1007/978-981-10-6674-0_12.</ref>.
 
Mitochondrial Lon protease interacts with '''[https://en.wikipedia.org/wiki/Chaperone_(protein) protein chaperone]''', notably [https://en.wikipedia.org/wiki/Chaperonin HSP60]-[https://en.wikipedia.org/wiki/Hsp70 Hsp70] complex to protect cell from apoptosis under environmental stress<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>.
 
The mitochondrial Lon protease is essentially found in the cytoplasmic of mitochondria because [https://en.wikipedia.org/wiki/Amino_acid amino-acid] has a potential mitochondrial targetting presequences<ref>García-Nafría, Javier, Gabriela Ondrovičová, Elena Blagova, Vladimir M Levdikov, Jacob A Bauer, Carolyn K Suzuki, Eva Kutejová, Anthony J Wilkinson, and Keith S Wilson. “Structure of the Catalytic Domain of the Human Mitochondrial Lon Protease: Proposed Relation of Oligomer Formation and Activity.” Protein Science : A Publication of the Protein Society 19, no. 5 (May 2010): 987–99. https://doi.org/10.1002/pro.376.</ref>.
 
Lon Human protease alternates between cycles of '''being bound to the mitochondrial genome''' and '''being free into the mitochondrial cytoplasm''' where it can degrade abnormal proteins coming from damaged proteins, errors in the synthesis, or [https://en.wikipedia.org/wiki/Protein_folding misfolded] of multimeric proteins. Its inactive conformation prevents uncontrolled proteolysis.
To achieve proteolytic cleavage, the Lon protein has to form a hexamer.
Lon protease has also a role in mtDNA quality control by permits oxidative mitochondrial DNA damage. Sensitivities of H2O2-induced mtDNA damage depend on the proportion of LON<ref>Lu, Bin. “Mitochondrial Lon Protease and Cancer.” Advances in Experimental Medicine and Biology 1038 (2017): 173–82. https://doi.org/10.1007/978-981-10-6674-0_12.</ref>.
Other ATP-dependent proteases are found in eukaryotic cells and organelles like [https://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex 26S protease] which uses [https://en.wikipedia.org/wiki/ATP_hydrolysis ATP hydrolysis] for conjugation or ubiquitin for example.
 

== General structure ==

Lon proteins are grouped into two families, '''LonA''' and '''LonB'''. The human protein LonP1 is part of the LonA proteins <ref>« The N-terminal domain plays a crucial role in the structure of a full-length human mitochondrial Lon protease | Scientific Reports ». Consulté le 13 janvier 2021. https://www.nature.com/articles/srep33631.
</ref>. This protein has three isoforms obtained by [https://en.wikipedia.org/wiki/Alternative_splicing alternative splicing] of the portion of DNA coding for this protein <ref>He, Lihong, Dongyang Luo, Fan Yang, Chunhao Li, Xuegong Zhang, Haiteng Deng, et Jing-Ren Zhang. « Multiple domains of bacterial and human Lon proteases define substrate selectivity ». Emerging Microbes & Infections 7 (17 août 2018). https://doi.org/10.1038/s41426-018-0148-4.
</ref>.
Globally there is a great diversity of Lon proteins, but they are all organised in an oligomeric ring structure, mostly hexameric structure with identical subunits.
Lon proteins are therefore an hexameric chambered [https://en.wikipedia.org/wiki/Protease protease] complex. (This structure is similar with yeast [https://www.yeastgenome.org/locus/S000000118 Pim1] )
The six Lon monomers are forming three pairs of legs owned by the N-terminal domain of the protein. This structure is emerging of the protein as a trimer of dimers <ref>Kutejová, Eva. « Mitochondrial Lon protease-unique structure and essential function in mammalian cells ». Integrative Cancer Science and Therapeutics 5, nᵒ 6 (2018). https://doi.org/10.15761/ICST.1000296.
</ref>.
 
Like many proteins, Lon is a '''flexible''' peptide which has different '''three-dimensional conformations'''. The protein can therefore pass from one conformation to another by hydrolysis of [https://biologydictionary.net/atp/ ATP].
With these conformational changes, the [https://en.wikipedia.org/wiki/Active_site '''active sites'''] of the Lon protein are protected from the external environment in the oligomeric complex that forms the '''degradation chamber'''.
This form of degradation chamber is also found in bacteria, plants, fungi and metazoan, the similarities with bacteria are most probably due to the [https://en.wikipedia.org/wiki/Symbiogenesis endosymbiotic theory].
 
 
This protein has a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] and [https://en.wikipedia.org/wiki/Chaperone_(protein) '''chaperone''']-like activity, it cannot unfold aggregated proteins, but can participate in the assembling of some complexes). These two enzymatic activities are separated on two polypeptide chains forming a complex or two separate domains on the same polypeptide chain.
 
The Lon protein has three main distinct domains: the first, the '''N-terminal''' domain, is specialised in '''substrate binding''' and [https://en.wikipedia.org/wiki/Oligomer '''oligomerization''']. The second, called the '''AAA+ domain''' (or A domain) corresponds to the fixation and hydrolysis site of the [https://biologydictionary.net/atp/ATP ATP]. Finally, the third domain located at the '''C-terminal''' is an active serine site leading to '''substrate degradation'''. This is a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] domain, called domain P <ref>He, Lihong, Dongyang Luo, Fan Yang, Chunhao Li, Xuegong Zhang, Haiteng Deng, et Jing-Ren Zhang. « Multiple domains of bacterial and human Lon proteases define substrate selectivity ». Emerging Microbes & Infections 7 (17 août 2018). https://doi.org/10.1038/s41426-018-0148-4.
</ref>.
 
Mammalian Lon protein only interacts with '''single-stranded DNA''' (ssDNA) but not dsDNA. There are therefore special sequences for interaction with '''G-rich DNA''' as well as RNA. In addition, the binding of a substrate to the protein stimulates the interaction with the DNA.
[https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] binds to the Lon protein with different affinities depending on the state of the cell and the type of cell meeting the following four parameters <ref>Lu, Bin, Swati Yadav, Parul G. Shah, Tong Liu, Bin Tian, Sebastian Pukszta, Nerissa Villaluna, et al. « Roles for the Human ATP-Dependent Lon Protease in Mitochondrial DNA Maintenance ». Journal of Biological Chemistry 282, nᵒ 24 (15 juin 2007): 17363‑74. https://doi.org/10.1074/jbc.M611540200.
</ref>:
 
- the single stranding state of mtDNA
 
- the bioavailability of the mtDNA binding sites
 
- the affinity of the protein for a given DNA sequence
 
- the total number of high and low affinity Lon binding sites present

== Structural highlights ==

== Evolutionary conservation ==

== Disease ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1644

2021-01-13T16:54:07Z

Camille Spicher:

{{Sandbox_Reserved_ESBS20_}}
==2x36 - Structure of the proteolytic domain of the Human Mitochondrial Lon protease==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

'''2x36''' is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This domain belongs to the [https://en.wikipedia.org/wiki/Lon_protease_family Lon protease family].
 
[https://en.wikipedia.org/wiki/Mitochondrion Mitochondrial] Lon [https://en.wikipedia.org/wiki/Protease protease] is an '''ATP-dependent serine protease''' involved in the selective degradation of abnormal proteins. [https://en.wikipedia.org/wiki/LONP1 LONP1] situated on chromosome 19 is the nuclear gene encoding mitochondrial Lon protein. The single species of [https://en.wikipedia.org/wiki/Messenger_RNA mRNA] of this protein is found in the mitochondrial matrix. This protein from human tissues has a molecular mass of 100 [https://en.wikipedia.org/wiki/Dalton_(unit) kDA].
 
== Function ==

The mitochondrial Lon protease is an important regulator of mitochondrial [https://en.wikipedia.org/wiki/Metabolism metabolism] including the maintenance and repair of mitochondrial [https://en.wikipedia.org/wiki/DNA DNA]. This protein is also essential for homeostasis of mitochondria, and by regulating some regulatory proteins which have a short life or damaged proteins.
 
Lon protease has three main roles.
This protein is able to do a '''[https://en.wikipedia.org/wiki/Proteolysis proteolytic] digestion''' of oxidized proteins which allows the renewal of essential mitochondrial enzymes such as [https://en.wikipedia.org/wiki/Aconitase aconitase] or [https://en.wikipedia.org/wiki/TFAM Mitochondrial transcription factor A].
Lon protease is involved in [https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] [https://en.wikipedia.org/wiki/DNA_replication replication] and [https://en.wikipedia.org/w/index.php?title=Mitogenesis&redirect=no mitogenesis] by being a '''mitochondrial [https://en.wikipedia.org/wiki/DNA-binding_protein DNA-bing protein]'''. Human Lon and mtDNA associate at the level of their at least 4 contiguous [https://en.wikipedia.org/wiki/Guanine guanine] sequence and form a [https://en.wikipedia.org/wiki/G-quadruplex G-quadruplex]<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>. This G-rich region is the control region for mtDNA replication and transcription<ref>Lu, Bin. “Mitochondrial Lon Protease and Cancer.” Advances in Experimental Medicine and Biology 1038 (2017): 173–82. https://doi.org/10.1007/978-981-10-6674-0_12.</ref>.
 
Mitochondrial Lon protease interacts with '''[https://en.wikipedia.org/wiki/Chaperone_(protein) protein chaperone]''', notably [https://en.wikipedia.org/wiki/Chaperonin HSP60]-[https://en.wikipedia.org/wiki/Hsp70 Hsp70] complex to protect cell from apoptosis under environmental stress<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>.
 
The mitochondrial Lon protease is essentially found in the cytoplasmic of mitochondria because [https://en.wikipedia.org/wiki/Amino_acid amino-acid] has a potential mitochondrial targetting presequences<ref>García-Nafría, Javier, Gabriela Ondrovičová, Elena Blagova, Vladimir M Levdikov, Jacob A Bauer, Carolyn K Suzuki, Eva Kutejová, Anthony J Wilkinson, and Keith S Wilson. “Structure of the Catalytic Domain of the Human Mitochondrial Lon Protease: Proposed Relation of Oligomer Formation and Activity.” Protein Science : A Publication of the Protein Society 19, no. 5 (May 2010): 987–99. https://doi.org/10.1002/pro.376.</ref>.
 
Lon Human protease alternates between cycles of '''being bound to the mitochondrial genome''' and '''being free into the mitochondrial cytoplasm''' where it can degrade abnormal proteins coming from damaged proteins, errors in the synthesis, or [https://en.wikipedia.org/wiki/Protein_folding misfolded] of multimeric proteins. Its inactive conformation prevents uncontrolled proteolysis.
To achieve proteolytic cleavage, the Lon protein has to form a hexamer.
Lon protease has also a role in mtDNA quality control by permits oxidative mitochondrial DNA damage. Sensitivities of H2O2-induced mtDNA damage depend on the proportion of LON<ref>Lu, Bin. “Mitochondrial Lon Protease and Cancer.” Advances in Experimental Medicine and Biology 1038 (2017): 173–82. https://doi.org/10.1007/978-981-10-6674-0_12.</ref>.
Other ATP-dependent proteases are found in eukaryotic cells and organelles like [https://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex 26S protease] which uses [https://en.wikipedia.org/wiki/ATP_hydrolysis ATP hydrolysis] for conjugation or ubiquitin for example.
 

== General structure ==

Lon proteins are grouped into two families, '''LonA''' and '''LonB'''. The human protein LonP1 is part of the LonA proteins <ref>« The N-terminal domain plays a crucial role in the structure of a full-length human mitochondrial Lon protease | Scientific Reports ». Consulté le 13 janvier 2021. https://www.nature.com/articles/srep33631.
</ref>. This protein has three isoforms obtained by [https://en.wikipedia.org/wiki/Alternative_splicing alternative splicing] of the portion of DNA coding for this protein <ref>He, Lihong, Dongyang Luo, Fan Yang, Chunhao Li, Xuegong Zhang, Haiteng Deng, et Jing-Ren Zhang. « Multiple domains of bacterial and human Lon proteases define substrate selectivity ». Emerging Microbes & Infections 7 (17 août 2018). https://doi.org/10.1038/s41426-018-0148-4.
</ref>.
Globally there is a great diversity of Lon proteins, but they are all organised in an oligomeric ring structure, mostly hexameric structure with identical subunits.
Lon proteins are therefore an hexameric chambered [https://en.wikipedia.org/wiki/Protease protease] complex. (This structure is similar with yeast [https://www.yeastgenome.org/locus/S000000118 Pim1] )
The six Lon monomers are forming three pairs of legs owned by the N-terminal domain of the protein. This structure is emerging of the protein as a trimer of dimers <ref>Kutejová, Eva. « Mitochondrial Lon protease-unique structure and essential function in mammalian cells ». Integrative Cancer Science and Therapeutics 5, nᵒ 6 (2018). https://doi.org/10.15761/ICST.1000296.
</ref>.
 
Like many proteins, Lon is a '''flexible''' peptide which has different '''three-dimensional conformations'''. The protein can therefore pass from one conformation to another by hydrolysis of [https://biologydictionary.net/atp/ ATP].
With these conformational changes, the [https://en.wikipedia.org/wiki/Active_site '''active sites'''] of the Lon protein are protected from the external environment in the oligomeric complex that forms the '''degradation chamber'''.
This form of degradation chamber is also found in bacteria, plants, fungi and metazoan, the similarities with bacteria are most probably due to the [https://en.wikipedia.org/wiki/Symbiogenesis endosymbiotic theory].
 
 
This protein has a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] and [https://en.wikipedia.org/wiki/Chaperone_(protein) '''chaperone''']-like activity, it cannot unfold aggregated proteins, but can participate in the assembling of some complexes). These two enzymatic activities are separated on two polypeptide chains forming a complex or two separate domains on the same polypeptide chain.
 
The Lon protein has three main distinct domains: the first, the '''N-terminal''' domain, is specialised in '''substrate binding''' and [https://en.wikipedia.org/wiki/Oligomer '''oligomerization''']. The second, called the '''AAA+ domain''' (or A domain) corresponds to the fixation and hydrolysis site of the [https://biologydictionary.net/atp/ATP ATP]. Finally, the third domain located at the '''C-terminal''' is an active serine site leading to '''substrate degradation'''. This is a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] domain, called domain P.
 
Mammalian Lon protein only interacts with '''single-stranded DNA''' (ssDNA) but not dsDNA. There are therefore special sequences for interaction with '''G-rich DNA''' as well as RNA. In addition, the binding of a substrate to the protein stimulates the interaction with the DNA.
[https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] binds to the Lon protein with different affinities depending on the state of the cell and the type of cell meeting the following four parameters <ref>Lu, Bin, Swati Yadav, Parul G. Shah, Tong Liu, Bin Tian, Sebastian Pukszta, Nerissa Villaluna, et al. « Roles for the Human ATP-Dependent Lon Protease in Mitochondrial DNA Maintenance ». Journal of Biological Chemistry 282, nᵒ 24 (15 juin 2007): 17363‑74. https://doi.org/10.1074/jbc.M611540200.
</ref>:
 
- the single stranding state of mtDNA
 
- the bioavailability of the mtDNA binding sites
 
- the affinity of the protein for a given DNA sequence
 
- the total number of high and low affinity Lon binding sites present

== Structural highlights ==

== Evolutionary conservation ==

== Disease ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1644

2021-01-13T16:51:08Z

Camille Spicher:

{{Sandbox_Reserved_ESBS20_}}
==2x36 - Structure of the proteolytic domain of the Human Mitochondrial Lon protease==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

'''2x36''' is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This domain belongs to the [https://en.wikipedia.org/wiki/Lon_protease_family Lon protease family].
 
[https://en.wikipedia.org/wiki/Mitochondrion Mitochondrial] Lon [https://en.wikipedia.org/wiki/Protease protease] is an '''ATP-dependent serine protease''' involved in the selective degradation of abnormal proteins. [https://en.wikipedia.org/wiki/LONP1 LONP1] situated on chromosome 19 is the nuclear gene encoding mitochondrial Lon protein. The single species of [https://en.wikipedia.org/wiki/Messenger_RNA mRNA] of this protein is found in the mitochondrial matrix. This protein from human tissues has a molecular mass of 100 [https://en.wikipedia.org/wiki/Dalton_(unit) kDA].
 
== Function ==

The mitochondrial Lon protease is an important regulator of mitochondrial [https://en.wikipedia.org/wiki/Metabolism metabolism] including the maintenance and repair of mitochondrial [https://en.wikipedia.org/wiki/DNA DNA]. This protein is also essential for homeostasis of mitochondria, and by regulating some regulatory proteins which have a short life or damaged proteins.
 
Lon protease has three main roles.
This protein is able to do a '''[https://en.wikipedia.org/wiki/Proteolysis proteolytic] digestion''' of oxidized proteins which allows the renewal of essential mitochondrial enzymes such as [https://en.wikipedia.org/wiki/Aconitase aconitase] or [https://en.wikipedia.org/wiki/TFAM Mitochondrial transcription factor A].
Lon protease is involved in [https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] [https://en.wikipedia.org/wiki/DNA_replication replication] and [https://en.wikipedia.org/w/index.php?title=Mitogenesis&redirect=no mitogenesis] by being a '''mitochondrial [https://en.wikipedia.org/wiki/DNA-binding_protein DNA-bing protein]'''. Human Lon and mtDNA associate at the level of their at least 4 contiguous [https://en.wikipedia.org/wiki/Guanine guanine] sequence and form a [https://en.wikipedia.org/wiki/G-quadruplex G-quadruplex]<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>. This G-rich region is the control region for mtDNA replication and transcription<ref>Lu, Bin. “Mitochondrial Lon Protease and Cancer.” Advances in Experimental Medicine and Biology 1038 (2017): 173–82. https://doi.org/10.1007/978-981-10-6674-0_12.</ref>.
 
Mitochondrial Lon protease interacts with '''[https://en.wikipedia.org/wiki/Chaperone_(protein) protein chaperone]''', notably [https://en.wikipedia.org/wiki/Chaperonin HSP60]-[https://en.wikipedia.org/wiki/Hsp70 Hsp70] complex to protect cell from apoptosis under environmental stress<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>.
 
The mitochondrial Lon protease is essentially found in the cytoplasmic of mitochondria because [https://en.wikipedia.org/wiki/Amino_acid amino-acid] has a potential mitochondrial targetting presequences<ref>García-Nafría, Javier, Gabriela Ondrovičová, Elena Blagova, Vladimir M Levdikov, Jacob A Bauer, Carolyn K Suzuki, Eva Kutejová, Anthony J Wilkinson, and Keith S Wilson. “Structure of the Catalytic Domain of the Human Mitochondrial Lon Protease: Proposed Relation of Oligomer Formation and Activity.” Protein Science : A Publication of the Protein Society 19, no. 5 (May 2010): 987–99. https://doi.org/10.1002/pro.376.</ref>.
 
Lon Human protease alternates between cycles of '''being bound to the mitochondrial genome''' and '''being free into the mitochondrial cytoplasm''' where it can degrade abnormal proteins coming from damaged proteins, errors in the synthesis, or [https://en.wikipedia.org/wiki/Protein_folding misfolded] of multimeric proteins. Its inactive conformation prevents uncontrolled proteolysis.
To achieve proteolytic cleavage, the Lon protein has to form a hexamer.
Lon protease has also a role in mtDNA quality control by permits oxidative mitochondrial DNA damage. Sensitivities of H2O2-induced mtDNA damage depend on the proportion of LON<ref>Lu, Bin. “Mitochondrial Lon Protease and Cancer.” Advances in Experimental Medicine and Biology 1038 (2017): 173–82. https://doi.org/10.1007/978-981-10-6674-0_12.</ref>.
Other ATP-dependent proteases are found in eukaryotic cells and organelles like [https://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex 26S protease] which uses [https://en.wikipedia.org/wiki/ATP_hydrolysis ATP hydrolysis] for conjugation or ubiquitin for example.
 

== General structure ==

Lon proteins are grouped into two families, '''LonA''' and '''LonB'''. The human protein LonP1 is part of the LonA proteins <ref>« The N-terminal domain plays a crucial role in the structure of a full-length human mitochondrial Lon protease | Scientific Reports ». Consulté le 13 janvier 2021. https://www.nature.com/articles/srep33631.
</ref>. This protein has three isoforms obtained by [https://en.wikipedia.org/wiki/Alternative_splicing alternative splicing] of the portion of DNA coding for this protein <ref>He, Lihong, Dongyang Luo, Fan Yang, Chunhao Li, Xuegong Zhang, Haiteng Deng, et Jing-Ren Zhang. « Multiple domains of bacterial and human Lon proteases define substrate selectivity ». Emerging Microbes & Infections 7 (17 août 2018). https://doi.org/10.1038/s41426-018-0148-4.
</ref>.
Globally there is a great diversity of Lon proteins, but they are all organised in an oligomeric ring structure, mostly hexameric structure with identical subunits.
Lon proteins are therefore an hexameric chambered [https://en.wikipedia.org/wiki/Protease protease] complex. (This structure is similar with yeast [https://www.yeastgenome.org/locus/S000000118 Pim1] )
The six Lon monomers are forming three pairs of legs owned by the N-terminal domain of the protein. This structure is emerging of the protein as a trimer of dimers <ref>Kutejová, Eva. « Mitochondrial Lon protease-unique structure and essential function in mammalian cells ». Integrative Cancer Science and Therapeutics 5, nᵒ 6 (2018). https://doi.org/10.15761/ICST.1000296.
</ref>.
 
Like many proteins, Lon is a '''flexible''' peptide which has different '''three-dimensional conformations'''. The protein can therefore pass from one conformation to another by hydrolysis of [https://biologydictionary.net/atp/ ATP].
With these conformational changes, the [https://en.wikipedia.org/wiki/Active_site '''active sites'''] of the Lon protein are protected from the external environment in the oligomeric complex that forms the '''degradation chamber'''.
This form of degradation chamber is also found in bacteria, plants, fungi and metazoan, the similarities with bacteria are most probably due to the [https://en.wikipedia.org/wiki/Symbiogenesis endosymbiotic theory].
 
 
This protein has a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] and [https://en.wikipedia.org/wiki/Chaperone_(protein) '''chaperone''']-like activity, it cannot unfold aggregated proteins, but can participate in the assembling of some complexes). These two enzymatic activities are separated on two polypeptide chains forming a complex or two separate domains on the same polypeptide chain.
 
The Lon protein has three main distinct domains: the first, the '''N-terminal''' domain, is specialised in '''substrate binding''' and [https://en.wikipedia.org/wiki/Oligomer '''oligomerization''']. The second, called the '''AAA+ domain''' (or A domain) corresponds to the fixation and hydrolysis site of the [https://biologydictionary.net/atp/ATP ATP]. Finally, the third domain located at the '''C-terminal''' is an active serine site leading to '''substrate degradation'''. This is a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] domain, called domain P.
 
Mammalian Lon protein only interacts with '''single-stranded DNA''' (ssDNA) but not dsDNA. There are therefore special sequences for interaction with '''G-rich DNA''' as well as RNA. In addition, the binding of a substrate to the protein stimulates the interaction with the DNA.
[https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] binds to the Lon protein with different affinities depending on the state of the cell and the type of cell meeting the following four parameters:
 
- the single stranding state of mtDNA
 
- the bioavailability of the mtDNA binding sites
 
- the affinity of the protein for a given DNA sequence
 
- the total number of high and low affinity Lon binding sites present

== Structural highlights ==

== Evolutionary conservation ==

== Disease ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1644

2021-01-13T16:48:10Z

Camille Spicher:

{{Sandbox_Reserved_ESBS20_}}
==2x36 - Structure of the proteolytic domain of the Human Mitochondrial Lon protease==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

'''2x36''' is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This domain belongs to the [https://en.wikipedia.org/wiki/Lon_protease_family Lon protease family].
 
[https://en.wikipedia.org/wiki/Mitochondrion Mitochondrial] Lon [https://en.wikipedia.org/wiki/Protease protease] is an '''ATP-dependent serine protease''' involved in the selective degradation of abnormal proteins. [https://en.wikipedia.org/wiki/LONP1 LONP1] situated on chromosome 19 is the nuclear gene encoding mitochondrial Lon protein. The single species of [https://en.wikipedia.org/wiki/Messenger_RNA mRNA] of this protein is found in the mitochondrial matrix. This protein from human tissues has a molecular mass of 100 [https://en.wikipedia.org/wiki/Dalton_(unit) kDA].
 
== Function ==

The mitochondrial Lon protease is an important regulator of mitochondrial [https://en.wikipedia.org/wiki/Metabolism metabolism] including the maintenance and repair of mitochondrial [https://en.wikipedia.org/wiki/DNA DNA]. This protein is also essential for homeostasis of mitochondria, and by regulating some regulatory proteins which have a short life or damaged proteins.
 
Lon protease has three main roles.
This protein is able to do a '''[https://en.wikipedia.org/wiki/Proteolysis proteolytic] digestion''' of oxidized proteins which allows the renewal of essential mitochondrial enzymes such as [https://en.wikipedia.org/wiki/Aconitase aconitase] or [https://en.wikipedia.org/wiki/TFAM Mitochondrial transcription factor A].
Lon protease is involved in [https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] [https://en.wikipedia.org/wiki/DNA_replication replication] and [https://en.wikipedia.org/w/index.php?title=Mitogenesis&redirect=no mitogenesis] by being a '''mitochondrial [https://en.wikipedia.org/wiki/DNA-binding_protein DNA-bing protein]'''. Human Lon and mtDNA associate at the level of their at least 4 contiguous [https://en.wikipedia.org/wiki/Guanine guanine] sequence and form a [https://en.wikipedia.org/wiki/G-quadruplex G-quadruplex]<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>. This G-rich region is the control region for mtDNA replication and transcription<ref>Lu, Bin. “Mitochondrial Lon Protease and Cancer.” Advances in Experimental Medicine and Biology 1038 (2017): 173–82. https://doi.org/10.1007/978-981-10-6674-0_12.</ref>.
 
Mitochondrial Lon protease interacts with '''[https://en.wikipedia.org/wiki/Chaperone_(protein) protein chaperone]''', notably [https://en.wikipedia.org/wiki/Chaperonin HSP60]-[https://en.wikipedia.org/wiki/Hsp70 Hsp70] complex to protect cell from apoptosis under environmental stress<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>.
 
The mitochondrial Lon protease is essentially found in the cytoplasmic of mitochondria because [https://en.wikipedia.org/wiki/Amino_acid amino-acid] has a potential mitochondrial targetting presequences<ref>García-Nafría, Javier, Gabriela Ondrovičová, Elena Blagova, Vladimir M Levdikov, Jacob A Bauer, Carolyn K Suzuki, Eva Kutejová, Anthony J Wilkinson, and Keith S Wilson. “Structure of the Catalytic Domain of the Human Mitochondrial Lon Protease: Proposed Relation of Oligomer Formation and Activity.” Protein Science : A Publication of the Protein Society 19, no. 5 (May 2010): 987–99. https://doi.org/10.1002/pro.376.</ref>.
 
Lon Human protease alternates between cycles of '''being bound to the mitochondrial genome''' and '''being free into the mitochondrial cytoplasm''' where it can degrade abnormal proteins coming from damaged proteins, errors in the synthesis, or [https://en.wikipedia.org/wiki/Protein_folding misfolded] of multimeric proteins. Its inactive conformation prevents uncontrolled proteolysis.
To achieve proteolytic cleavage, the Lon protein has to form a hexamer.
Lon protease has also a role in mtDNA quality control by permits oxidative mitochondrial DNA damage. Sensitivities of H2O2-induced mtDNA damage depend on the proportion of LON<ref>Lu, Bin. “Mitochondrial Lon Protease and Cancer.” Advances in Experimental Medicine and Biology 1038 (2017): 173–82. https://doi.org/10.1007/978-981-10-6674-0_12.</ref>.
Other ATP-dependent proteases are found in eukaryotic cells and organelles like [https://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex 26S protease] which uses [https://en.wikipedia.org/wiki/ATP_hydrolysis ATP hydrolysis] for conjugation or ubiquitin for example.
 

== General structure ==

Lon proteins are grouped into two families, '''LonA''' and '''LonB'''. The human protein LonP1 is part of the LonA proteins <ref>« The N-terminal domain plays a crucial role in the structure of a full-length human mitochondrial Lon protease | Scientific Reports ». Consulté le 13 janvier 2021. https://www.nature.com/articles/srep33631.
</ref>. This protein has three isoforms obtained by [https://en.wikipedia.org/wiki/Alternative_splicing alternative splicing] of the portion of DNA coding for this protein <ref>He, Lihong, Dongyang Luo, Fan Yang, Chunhao Li, Xuegong Zhang, Haiteng Deng, et Jing-Ren Zhang. « Multiple domains of bacterial and human Lon proteases define substrate selectivity ». Emerging Microbes & Infections 7 (17 août 2018). https://doi.org/10.1038/s41426-018-0148-4.
</ref>.
Globally there is a great diversity of Lon proteins, but they are all organised in an oligomeric ring structure, mostly hexameric structure with identical subunits.
Lon proteins are therefore an hexameric chambered [https://en.wikipedia.org/wiki/Protease protease] complex. (This structure is similar with yeast [https://www.yeastgenome.org/locus/S000000118 Pim1] )
The six Lon monomers are forming three pairs of legs owned by the N-terminal domain of the protein. This structure is emerging of the protein as a trimer of dimers.
 
Like many proteins, Lon is a '''flexible''' peptide which has different '''three-dimensional conformations'''. The protein can therefore pass from one conformation to another by hydrolysis of [https://biologydictionary.net/atp/ ATP].
With these conformational changes, the [https://en.wikipedia.org/wiki/Active_site '''active sites'''] of the Lon protein are protected from the external environment in the oligomeric complex that forms the '''degradation chamber'''.
This form of degradation chamber is also found in bacteria, plants, fungi and metazoan, the similarities with bacteria are most probably due to the [https://en.wikipedia.org/wiki/Symbiogenesis endosymbiotic theory].
 
 
This protein has a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] and [https://en.wikipedia.org/wiki/Chaperone_(protein) '''chaperone''']-like activity, it cannot unfold aggregated proteins, but can participate in the assembling of some complexes). These two enzymatic activities are separated on two polypeptide chains forming a complex or two separate domains on the same polypeptide chain.
 
The Lon protein has three main distinct domains: the first, the '''N-terminal''' domain, is specialised in '''substrate binding''' and [https://en.wikipedia.org/wiki/Oligomer '''oligomerization''']. The second, called the '''AAA+ domain''' (or A domain) corresponds to the fixation and hydrolysis site of the [https://biologydictionary.net/atp/ATP ATP]. Finally, the third domain located at the '''C-terminal''' is an active serine site leading to '''substrate degradation'''. This is a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] domain, called domain P.
 
Mammalian Lon protein only interacts with '''single-stranded DNA''' (ssDNA) but not dsDNA. There are therefore special sequences for interaction with '''G-rich DNA''' as well as RNA. In addition, the binding of a substrate to the protein stimulates the interaction with the DNA.
[https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] binds to the Lon protein with different affinities depending on the state of the cell and the type of cell meeting the following four parameters:
 
- the single stranding state of mtDNA
 
- the bioavailability of the mtDNA binding sites
 
- the affinity of the protein for a given DNA sequence
 
- the total number of high and low affinity Lon binding sites present

== Structural highlights ==

== Evolutionary conservation ==

== Disease ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1644

2021-01-13T16:41:51Z

Camille Spicher:

{{Sandbox_Reserved_ESBS20_}}
==2x36 - Structure of the proteolytic domain of the Human Mitochondrial Lon protease==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

'''2x36''' is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This domain belongs to the [https://en.wikipedia.org/wiki/Lon_protease_family Lon protease family].
 
[https://en.wikipedia.org/wiki/Mitochondrion Mitochondrial] Lon [https://en.wikipedia.org/wiki/Protease protease] is an '''ATP-dependent serine protease''' involved in the selective degradation of abnormal proteins. [https://en.wikipedia.org/wiki/LONP1 LONP1] situated on chromosome 19 is the nuclear gene encoding mitochondrial Lon protein. The single species of [https://en.wikipedia.org/wiki/Messenger_RNA mRNA] of this protein is found in the mitochondrial matrix. This protein from human tissues has a molecular mass of 100 [https://en.wikipedia.org/wiki/Dalton_(unit) kDA].
 
== Function ==

The mitochondrial Lon protease is an important regulator of mitochondrial [https://en.wikipedia.org/wiki/Metabolism metabolism] including the maintenance and repair of mitochondrial [https://en.wikipedia.org/wiki/DNA DNA]. This protein is also essential for homeostasis of mitochondria, and by regulating some regulatory proteins which have a short life or damaged proteins.
 
Lon protease has three main roles.
This protein is able to do a '''[https://en.wikipedia.org/wiki/Proteolysis proteolytic] digestion''' of oxidized proteins which allows the renewal of essential mitochondrial enzymes such as [https://en.wikipedia.org/wiki/Aconitase aconitase] or [https://en.wikipedia.org/wiki/TFAM Mitochondrial transcription factor A].
Lon protease is involved in [https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] [https://en.wikipedia.org/wiki/DNA_replication replication] and [https://en.wikipedia.org/w/index.php?title=Mitogenesis&redirect=no mitogenesis] by being a '''mitochondrial [https://en.wikipedia.org/wiki/DNA-binding_protein DNA-bing protein]'''. Human Lon and mtDNA associate at the level of their at least 4 contiguous [https://en.wikipedia.org/wiki/Guanine guanine] sequence and form a [https://en.wikipedia.org/wiki/G-quadruplex G-quadruplex]<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>. This G-rich region is the control region for mtDNA replication and transcription<ref>Lu, Bin. “Mitochondrial Lon Protease and Cancer.” Advances in Experimental Medicine and Biology 1038 (2017): 173–82. https://doi.org/10.1007/978-981-10-6674-0_12.</ref>.

Mitochondrial Lon protease interacts with '''[https://en.wikipedia.org/wiki/Chaperone_(protein) protein chaperone]''', notably [https://en.wikipedia.org/wiki/Chaperonin HSP60]-[https://en.wikipedia.org/wiki/Hsp70 Hsp70] complex to protect cell from apoptosis under environmental stress<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>.
 
The mitochondrial Lon protease is essentially found in the cytoplasmic of mitochondria because [https://en.wikipedia.org/wiki/Amino_acid amino-acid] has a potential mitochondrial targetting presequences<ref>García-Nafría, Javier, Gabriela Ondrovičová, Elena Blagova, Vladimir M Levdikov, Jacob A Bauer, Carolyn K Suzuki, Eva Kutejová, Anthony J Wilkinson, and Keith S Wilson. “Structure of the Catalytic Domain of the Human Mitochondrial Lon Protease: Proposed Relation of Oligomer Formation and Activity.” Protein Science : A Publication of the Protein Society 19, no. 5 (May 2010): 987–99. https://doi.org/10.1002/pro.376.</ref>.

Lon Human protease alternates between cycles of '''being bound to the mitochondrial genome''' and '''being free into the mitochondrial cytoplasm''' where it can degrade abnormal proteins coming from damaged proteins, errors in the synthesis, or [https://en.wikipedia.org/wiki/Protein_folding misfolded] of multimeric proteins. Its inactive conformation prevents uncontrolled proteolysis.
To achieve proteolytic cleavage, the Lon protein has to form a hexamer.
Lon protease has also a role in mtDNA quality control by permits oxidative mitochondrial DNA damage. Sensitivities of H2O2-induced mtDNA damage depend on the proportion of LON<ref>Lu, Bin. “Mitochondrial Lon Protease and Cancer.” Advances in Experimental Medicine and Biology 1038 (2017): 173–82. https://doi.org/10.1007/978-981-10-6674-0_12.</ref>.
Other ATP-dependent proteases are found in eukaryotic cells and organelles like [https://en.wikipedia.org/wiki/Proteasome_endopeptidase_complex 26S protease] which uses [https://en.wikipedia.org/wiki/ATP_hydrolysis ATP hydrolysis] for conjugation or ubiquitin for example.

== General structure ==

Lon proteins are grouped into two families, '''LonA''' and '''LonB'''. The human protein LonP1 is part of the LonA proteins <ref>« The N-terminal domain plays a crucial role in the structure of a full-length human mitochondrial Lon protease | Scientific Reports ». Consulté le 13 janvier 2021. https://www.nature.com/articles/srep33631.
</ref>. This protein has three isoforms obtained by [https://en.wikipedia.org/wiki/Alternative_splicing alternative splicing] of the portion of DNA coding for this protein.
Globally there is a great diversity of Lon proteins, but they are all organised in an oligomeric ring structure, mostly hexameric structure with identical subunits.
Lon proteins are therefore an hexameric chambered [https://en.wikipedia.org/wiki/Protease protease] complex. (This structure is similar with yeast [https://www.yeastgenome.org/locus/S000000118 Pim1] )
The six Lon monomers are forming three pairs of legs owned by the N-terminal domain of the protein. This structure is emerging of the protein as a trimer of dimers.
 
Like many proteins, Lon is a '''flexible''' peptide which has different '''three-dimensional conformations'''. The protein can therefore pass from one conformation to another by hydrolysis of [https://biologydictionary.net/atp/ ATP].
With these conformational changes, the [https://en.wikipedia.org/wiki/Active_site '''active sites'''] of the Lon protein are protected from the external environment in the oligomeric complex that forms the '''degradation chamber'''.
This form of degradation chamber is also found in bacteria, plants, fungi and metazoan, the similarities with bacteria are most probably due to the [https://en.wikipedia.org/wiki/Symbiogenesis endosymbiotic theory].
 
 
This protein has a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] and [https://en.wikipedia.org/wiki/Chaperone_(protein) '''chaperone''']-like activity, it cannot unfold aggregated proteins, but can participate in the assembling of some complexes). These two enzymatic activities are separated on two polypeptide chains forming a complex or two separate domains on the same polypeptide chain.
 
The Lon protein has three main distinct domains: the first, the '''N-terminal''' domain, is specialised in '''substrate binding''' and [https://en.wikipedia.org/wiki/Oligomer '''oligomerization''']. The second, called the '''AAA+ domain''' (or A domain) corresponds to the fixation and hydrolysis site of the [https://biologydictionary.net/atp/ATP ATP]. Finally, the third domain located at the '''C-terminal''' is an active serine site leading to '''substrate degradation'''. This is a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] domain, called domain P.
 
Mammalian Lon protein only interacts with '''single-stranded DNA''' (ssDNA) but not dsDNA. There are therefore special sequences for interaction with '''G-rich DNA''' as well as RNA. In addition, the binding of a substrate to the protein stimulates the interaction with the DNA.
[https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] binds to the Lon protein with different affinities depending on the state of the cell and the type of cell meeting the following four parameters:
 
- the single stranding state of mtDNA
 
- the bioavailability of the mtDNA binding sites
 
- the affinity of the protein for a given DNA sequence
 
- the total number of high and low affinity Lon binding sites present

== Structural highlights ==

== Evolutionary conservation ==

== Disease ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1644

2021-01-13T16:38:35Z

Camille Spicher:

{{Sandbox_Reserved_ESBS20_}}
==2x36 - Structure of the proteolytic domain of the Human Mitochondrial Lon protease==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

'''2x36''' is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This domain belongs to the [https://en.wikipedia.org/wiki/Lon_protease_family Lon protease family].
 
[https://en.wikipedia.org/wiki/Mitochondrion Mitochondrial] Lon [https://en.wikipedia.org/wiki/Protease protease] is an '''ATP-dependent serine protease''' involved in the selective degradation of abnormal proteins. [https://en.wikipedia.org/wiki/LONP1 LONP1] situated on chromosome 19 is the nuclear gene encoding mitochondrial Lon protein. The single species of [https://en.wikipedia.org/wiki/Messenger_RNA mRNA] of this protein is found in the mitochondrial matrix. This protein from human tissues has a molecular mass of 100 [https://en.wikipedia.org/wiki/Dalton_(unit) kDA].
 
== Function ==

The mitochondrial Lon protease is an important regulator of mitochondrial [https://en.wikipedia.org/wiki/Metabolism metabolism] including the maintenance and repair of mitochondrial [https://en.wikipedia.org/wiki/DNA DNA]. This protein is also essential for homeostasis of mitochondria, and by regulating some regulatory proteins which have a short life or damaged proteins.
 
Lon protease has three main roles.
This protein is able to do a '''[https://en.wikipedia.org/wiki/Proteolysis proteolytic] digestion''' of oxidized proteins which allows the renewal of essential mitochondrial enzymes such as [https://en.wikipedia.org/wiki/Aconitase aconitase] or [https://en.wikipedia.org/wiki/TFAM Mitochondrial transcription factor A].
Lon protease is involved in [https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] [https://en.wikipedia.org/wiki/DNA_replication replication] and [https://en.wikipedia.org/w/index.php?title=Mitogenesis&redirect=no mitogenesis] by being a '''mitochondrial [https://en.wikipedia.org/wiki/DNA-binding_protein DNA-bing protein]'''. Human Lon and mtDNA associate at the level of their 4 contiguous [https://en.wikipedia.org/wiki/Guanine guanine] sequence and form a [https://en.wikipedia.org/wiki/G-quadruplex G-quadruplex]<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>.

Mitochondrial Lon protease interacts with [https://en.wikipedia.org/wiki/Chaperone_(protein) protein chaperone], notably [https://en.wikipedia.org/wiki/Chaperonin HSP60]-[https://en.wikipedia.org/wiki/Hsp70 Hsp70] complex to protect cell from apoptosis under environmental stress<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>.
 
The mitochondrial Lon protease is essentially found in the cytoplasmic of mitochondria because [https://en.wikipedia.org/wiki/Amino_acid amino-acid] has a potential mitochondrial targetting presequences<ref>García-Nafría, Javier, Gabriela Ondrovičová, Elena Blagova, Vladimir M Levdikov, Jacob A Bauer, Carolyn K Suzuki, Eva Kutejová, Anthony J Wilkinson, and Keith S Wilson. “Structure of the Catalytic Domain of the Human Mitochondrial Lon Protease: Proposed Relation of Oligomer Formation and Activity.” Protein Science : A Publication of the Protein Society 19, no. 5 (May 2010): 987–99. https://doi.org/10.1002/pro.376.</ref>.

== General structure ==

Lon proteins are grouped into two families, '''LonA''' and '''LonB'''. The human protein LonP1 is part of the LonA proteins. This protein has three isoforms obtained by [https://en.wikipedia.org/wiki/Alternative_splicing alternative splicing] of the portion of DNA coding for this protein.
Globally there is a great diversity of Lon proteins, but they are all organised in an oligomeric ring structure, mostly hexameric structure with identical subunits.
Lon proteins are therefore an hexameric chambered [https://en.wikipedia.org/wiki/Protease protease] complex. (This structure is similar with yeast [https://www.yeastgenome.org/locus/S000000118 Pim1] )
The six Lon monomers are forming three pairs of legs owned by the N-terminal domain of the protein. This structure is emerging of the protein as a trimer of dimers.
 
Like many proteins, Lon is a '''flexible''' peptide which has different '''three-dimensional conformations'''. The protein can therefore pass from one conformation to another by hydrolysis of [https://biologydictionary.net/atp/ ATP].
With these conformational changes, the [https://en.wikipedia.org/wiki/Active_site '''active sites'''] of the Lon protein are protected from the external environment in the oligomeric complex that forms the '''degradation chamber'''.
This form of degradation chamber is also found in bacteria, plants, fungi and metazoan, the similarities with bacteria are most probably due to the [https://en.wikipedia.org/wiki/Symbiogenesis endosymbiotic theory].
 
 
This protein has a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] and [https://en.wikipedia.org/wiki/Chaperone_(protein) '''chaperone''']-like activity, it cannot unfold aggregated proteins, but can participate in the assembling of some complexes). These two enzymatic activities are separated on two polypeptide chains forming a complex or two separate domains on the same polypeptide chain.
 
The Lon protein has three main distinct domains: the first, the '''N-terminal''' domain, is specialised in '''substrate binding''' and [https://en.wikipedia.org/wiki/Oligomer '''oligomerization''']. The second, called the '''AAA+ domain''' (or A domain) corresponds to the fixation and hydrolysis site of the [https://biologydictionary.net/atp/ATP ATP]. Finally, the third domain located at the '''C-terminal''' is an active serine site leading to '''substrate degradation'''. This is a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] domain, called domain P.
 
Mammalian Lon protein only interacts with '''single-stranded DNA''' (ssDNA) but not dsDNA. There are therefore special sequences for interaction with '''G-rich DNA''' as well as RNA. In addition, the binding of a substrate to the protein stimulates the interaction with the DNA.
[https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] binds to the Lon protein with different affinities depending on the state of the cell and the type of cell meeting the following four parameters:
 
- the single stranding state of mtDNA
 
- the bioavailability of the mtDNA binding sites
 
- the affinity of the protein for a given DNA sequence
 
- the total number of high and low affinity Lon binding sites present

== Structural highlights ==

== Evolutionary conservation ==

== Disease ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1644

2021-01-13T16:37:24Z

Camille Spicher:

{{Sandbox_Reserved_ESBS20_}}
==2x36 - Structure of the proteolytic domain of the Human Mitochondrial Lon protease==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

'''2x36''' is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This domain belongs to the [https://en.wikipedia.org/wiki/Lon_protease_family Lon protease family].
 
[https://en.wikipedia.org/wiki/Mitochondrion Mitochondrial] Lon [https://en.wikipedia.org/wiki/Protease protease] is an '''ATP-dependent serine protease''' involved in the selective degradation of abnormal proteins. [https://en.wikipedia.org/wiki/LONP1 LONP1] situated on chromosome 19 is the nuclear gene encoding mitochondrial Lon protein. The single species of [https://en.wikipedia.org/wiki/Messenger_RNA mRNA] of this protein is found in the mitochondrial matrix. This protein from human tissues has a molecular mass of 100 [https://en.wikipedia.org/wiki/Dalton_(unit) kDA].
 
== Function ==

The mitochondrial Lon protease is an important regulator of mitochondrial [https://en.wikipedia.org/wiki/Metabolism metabolism] including the maintenance and repair of mitochondrial [https://en.wikipedia.org/wiki/DNA DNA]. This protein is also essential for homeostasis of mitochondria, and by regulating some regulatory proteins which have a short life or damaged proteins.
 
Lon protease has three main roles.
This protein is able to do a '''[https://en.wikipedia.org/wiki/Proteolysis proteolytic] digestion''' of oxidized proteins which allows the renewal of essential mitochondrial enzymes such as [https://en.wikipedia.org/wiki/Aconitase aconitase] or [https://en.wikipedia.org/wiki/TFAM Mitochondrial transcription factor A].
Lon protease is involved in [https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] [https://en.wikipedia.org/wiki/DNA_replication replication] and [https://en.wikipedia.org/w/index.php?title=Mitogenesis&redirect=no mitogenesis] by being a '''mitochondrial [https://en.wikipedia.org/wiki/DNA-binding_protein DNA-bing protein]'''. Human Lon and mtDNA associate at the level of their 4 contiguous [https://en.wikipedia.org/wiki/Guanine guanine] sequence and form a [https://en.wikipedia.org/wiki/G-quadruplex G-quadruplex]<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>.

Mitochondrial Lon protease interacts with [https://en.wikipedia.org/wiki/Chaperone_(protein) protein chaperone], notably [https://en.wikipedia.org/wiki/Chaperonin HSP60]-[https://en.wikipedia.org/wiki/Hsp70 Hsp70] complex to protect cell from apoptosis under environmental stress<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>.
 
The mitochondrial Lon protease is essentially found in the cytoplasmic of mitochondria because [https://en.wikipedia.org/wiki/Amino_acid amino-acid] has a potential mitochondrial targetting presequences<ref>García-Nafría, Javier, Gabriela Ondrovičová, Elena Blagova, Vladimir M Levdikov, Jacob A Bauer, Carolyn K Suzuki, Eva Kutejová, Anthony J Wilkinson, and Keith S Wilson. “Structure of the Catalytic Domain of the Human Mitochondrial Lon Protease: Proposed Relation of Oligomer Formation and Activity.” Protein Science : A Publication of the Protein Society 19, no. 5 (May 2010): 987–99. https://doi.org/10.1002/pro.376.</ref>.

== General structure ==

Lon proteins are grouped into two families, '''LonA''' and '''LonB'''. The human protein LonP1 is part of the LonA proteins. This protein has three isoforms obtained by [https://en.wikipedia.org/wiki/Alternative_splicing alternative splicing] of the portion of DNA coding for this protein.
Globally there is a great diversity of Lon proteins, but they are all organised in an oligomeric ring structure, mostly hexameric structure with identical subunits.
Lon proteins are therefore an hexameric chambered [https://en.wikipedia.org/wiki/Protease protease] complex. (This structure is similar with yeast [https://www.yeastgenome.org/locus/S000000118 Pim1] )
The six Lon monomers are forming three pairs of legs owned by the N-terminal domain of the protein. This structure is emerging of the protein as a trimer of dimers.
 
Like many proteins, Lon is a '''flexible''' peptide which has different '''three-dimensional conformations'''. The protein can therefore pass from one conformation to another by hydrolysis of [https://biologydictionary.net/atp/ ATP].
With these conformational changes, the [https://en.wikipedia.org/wiki/Active_site '''active sites'''] of the Lon protein are protected from the external environment in the oligomeric complex that forms the '''degradation chamber'''.
This form of degradation chamber is also found in bacteria, plants, fungi and metazoan, the similarities with bacteria are most probably due to the [https://en.wikipedia.org/wiki/Symbiogenesis endosymbiotic theory].
 
 
This protein has a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] and [https://en.wikipedia.org/wiki/Chaperone_(protein) '''chaperone''']-like activity, it cannot unfold aggregated proteins, but can participate in the assembling of some complexes). These two enzymatic activities are separated on two polypeptide chains forming a complex or two separate domains on the same polypeptide chain.
 
The Lon protein has three main distinct domains: the first, the '''N-terminal''' domain, is specialised in '''substrate binding''' and [https://en.wikipedia.org/wiki/Oligomer '''oligomerization''']. The second, called the '''AAA+ domain''' (or A domain) corresponds to the fixation and hydrolysis site of the [https://biologydictionary.net/atp/ATP ATP]. Finally, the third domain located at the '''C-terminal''' is an active serine site leading to '''substrate degradation'''. This is a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] domain, called domain P.
 
Mammalian Lon protein only interacts with single-stranded DNA (ssDNA) but not dsDNA. There are therefore special sequences for interaction with G-rich DNA as well as RNA. In addition, the binding of a substrate to the protein stimulates the interaction with the DNA.
[https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] binds to the Lon protein with different affinities depending on the state of the cell and the type of cell meeting the following four parameters:
 
- the single stranding state of mtDNA
 
- the bioavailability of the mtDNA binding sites
 
- the affinity of the protein for a given DNA sequence
 
- the total number of high and low affinity Lon binding sites present

== Structural highlights ==

== Evolutionary conservation ==

== Disease ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

Sandbox Reserved 1644

2021-01-13T16:36:31Z

Camille Spicher:

{{Sandbox_Reserved_ESBS20_}}
==2x36 - Structure of the proteolytic domain of the Human Mitochondrial Lon protease==
<StructureSection load='1stp' size='340' side='right' caption='Caption for this structure' scene=''>
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.

'''2x36''' is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This domain belongs to the [https://en.wikipedia.org/wiki/Lon_protease_family Lon protease family].
 
[https://en.wikipedia.org/wiki/Mitochondrion Mitochondrial] Lon [https://en.wikipedia.org/wiki/Protease protease] is an '''ATP-dependent serine protease''' involved in the selective degradation of abnormal proteins. [https://en.wikipedia.org/wiki/LONP1 LONP1] situated on chromosome 19 is the nuclear gene encoding mitochondrial Lon protein. The single species of [https://en.wikipedia.org/wiki/Messenger_RNA mRNA] of this protein is found in the mitochondrial matrix. This protein from human tissues has a molecular mass of 100 [https://en.wikipedia.org/wiki/Dalton_(unit) kDA].
 
== Function ==

The mitochondrial Lon protease is an important regulator of mitochondrial [https://en.wikipedia.org/wiki/Metabolism metabolism] including the maintenance and repair of mitochondrial [https://en.wikipedia.org/wiki/DNA DNA]. This protein is also essential for homeostasis of mitochondria, and by regulating some regulatory proteins which have a short life or damaged proteins.
 
Lon protease has three main roles.
This protein is able to do a '''[https://en.wikipedia.org/wiki/Proteolysis proteolytic] digestion''' of oxidized proteins which allows the renewal of essential mitochondrial enzymes such as [https://en.wikipedia.org/wiki/Aconitase aconitase] or [https://en.wikipedia.org/wiki/TFAM Mitochondrial transcription factor A].
Lon protease is involved in [https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] [https://en.wikipedia.org/wiki/DNA_replication replication] and [https://en.wikipedia.org/w/index.php?title=Mitogenesis&redirect=no mitogenesis] by being a '''mitochondrial [https://en.wikipedia.org/wiki/DNA-binding_protein DNA-bing protein]'''. Human Lon and mtDNA associate at the level of their 4 contiguous [https://en.wikipedia.org/wiki/Guanine guanine] sequence and form a [https://en.wikipedia.org/wiki/G-quadruplex G-quadruplex]<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>.

Mitochondrial Lon protease interacts with [https://en.wikipedia.org/wiki/Chaperone_(protein) protein chaperone], notably [https://en.wikipedia.org/wiki/Chaperonin HSP60]-[https://en.wikipedia.org/wiki/Hsp70 Hsp70] complex to protect cell from apoptosis under environmental stress<ref>Bota, Daniela A., and Kelvin J. A. Davies. “Mitochondrial Lon Protease in Human Disease and Aging: Including an Etiologic Classification of Lon-Related Diseases and Disorders.” Free Radical Biology & Medicine 100 (November 2016): 188–98. https://doi.org/10.1016/j.freeradbiomed.2016.06.031.</ref>.
 
The mitochondrial Lon protease is essentially found in the cytoplasmic of mitochondria because [https://en.wikipedia.org/wiki/Amino_acid amino-acid] has a potential mitochondrial targetting presequences<ref>García-Nafría, Javier, Gabriela Ondrovičová, Elena Blagova, Vladimir M Levdikov, Jacob A Bauer, Carolyn K Suzuki, Eva Kutejová, Anthony J Wilkinson, and Keith S Wilson. “Structure of the Catalytic Domain of the Human Mitochondrial Lon Protease: Proposed Relation of Oligomer Formation and Activity.” Protein Science : A Publication of the Protein Society 19, no. 5 (May 2010): 987–99. https://doi.org/10.1002/pro.376.</ref>.

== General structure ==

Lon proteins are grouped into two families, '''LonA''' and '''LonB'''. The human protein LonP1 is part of the LonA proteins. This protein has three isoforms obtained by [https://en.wikipedia.org/wiki/Alternative_splicing alternative splicing] of the portion of DNA coding for this protein.
Globally there is a great diversity of Lon proteins, but they are all organised in an oligomeric ring structure, mostly hexameric structure with identical subunits.
Lon proteins are therefore an hexameric chambered [https://en.wikipedia.org/wiki/Protease protease] complex. (This structure is similar with yeast [https://www.yeastgenome.org/locus/S000000118 Pim1] )
The six Lon monomers are forming three pairs of legs owned by the N-terminal domain of the protein. This structure is emerging of the protein as a trimer of dimers.
 
Like many proteins, Lon is a '''flexible''' peptide which has different '''three-dimensional conformations'''. The protein can therefore pass from one conformation to another by hydrolysis of [https://biologydictionary.net/atp/ ATP].
With these conformational changes, the [https://en.wikipedia.org/wiki/Active_site '''active sites'''] of the Lon protein are protected from the external environment in the oligomeric complex that forms the '''degradation chamber'''.
This form of degradation chamber is also found in bacteria, plants, fungi and metazoan, the similarities with bacteria are most probably due to the [https://en.wikipedia.org/wiki/Symbiogenesis endosymbiotic theory].
 
 
This protein has a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] and [https://en.wikipedia.org/wiki/Chaperone_(protein) '''chaperone''']-like activity, it cannot unfold aggregated proteins, but can participate in the assembling of some complexes). These two enzymatic activities are separated on two polypeptide chains forming a complex or two separate domains on the same polypeptide chain.
 
The Lon protein has three main distinct domains: the first, the '''N-terminal''' domain, is specialised in '''substrate binding''' and [https://en.wikipedia.org/wiki/Oligomer '''oligomerization''']. The second, called the '''AAA+ domain''' (or A domain) corresponds to the fixation and hydrolysis site of the [https://biologydictionary.net/atp/ATP ATP]. Finally, the third domain located at the '''C-terminal''' is an active serine site leading to '''substrate degradation'''. This is a [https://en.wikipedia.org/wiki/Proteolysis '''proteolytic'''] domain, called domain P.
 
Mammalian Lon protein only interacts with single-stranded DNA (ssDNA) but not dsDNA. There are therefore special sequences for interaction with G-rich DNA as well as RNA. In addition, the binding of a substrate to the protein stimulates the interaction with the DNA.
[https://en.wikipedia.org/wiki/Mitochondrial_DNA mtDNA] binds to the Lon protein with different affinities depending on the state of the cell and the type of cell meeting the following four parameters:
- the single stranding state of mtDNA
- the bioavailability of the mtDNA binding sites
- the affinity of the protein for a given DNA sequence
- the total number of high and low affinity Lon binding sites present

== Structural highlights ==

== Evolutionary conservation ==

== Disease ==

This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

</StructureSection>
== References ==
<references/>

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