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| <scene name='75/752263/3wtp/2'>Text To Be Displayed</scene>'''Histone H3.3'''
| | ==Kinesin Motor Domain== |
| <StructureSection load='3WTP' size='340' side='right' caption='Caption for this structure' scene=''> | | <StructureSection load='1bg2' size='340' side='right' caption='Kinesin Protein' scene=''> |
| This is a default text for your page '''Sandbox GGC1'''. Click above on '''edit this page''' to modify. Be careful with the < and > signs.
| | Kinesin is an ATP-dependent motor protein responsible for the transportation of cargo. It is a heterotetramer composed of light and heavy chains. |
| 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.
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| == Function == | | == '''Function''' == |
| [https://www.uniprot.org/uniprot/P84243 histone H3] replaces H3 in a range of nucleosomes in active genes and it takes over the original H3 in non dividing cells. Nucleosomes wrap around and compact DNA into chromatin which limits DNA access to cellular machineries which need DNA as a template. Histones play an important role in regulation of transcription, DNA repair, DNA replication and also chromosomal stability. Access to DNA is regulated by post-translational modifications of histones which is called a histone code, and nucleosome remodeling. It also serves as a replacement histone that's imbedded chromatin regions by the HIRA chaperone, after the depletion of the H3.1 during transcription and DNA repair.
| | * Moving cargo usually from the center of the cell to the margins <br/> |
| == Disease ==
| | * Involved in cell replication and axonal signaling |
| There have been studies that have identified mutations encoding a K27M substitution and there have also been mutations that encoded
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| GLY 34 to ARG or VAL called the G34R/V substitution. There are mutations in H3.3 that are found in different types of bone tumors like [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446520/ chrondroblastoma] for example and giant cell tumors of the bone. [https://cancerdiscovery.aacrjournals.org/content/3/12/1329.1 Chondroblastoma] arises in children and in young adults in the cartilage of the growth plates of the long bones and is most typically benign.
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| [[Image:Glioma_2018_1_4_117_240231_f1.jpg]]
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| [[Image:a00609f01_resize.jpg]]
| | == '''Disease''' == |
| | *Charcot Marie Tooth (CMT): Charcot Marie Tooth is one of many diseases that affect the peripheral nervous system. Individuals may suffer physical disabilities due to weakness in transmission of signals firing from the central nervous system |
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| == Relevance ==
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| Histone octamer containing two of H2A, H2B, H3 and H4 and the octamer wraps 147bp of DNA. H3.3 interacts with HIRA which is a chaperone and ZMYND11 when trimethylated at <scene name='75/752263/3wtp/2'>Lysine-36</scene>
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| == Structural highlights ==
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| in a PubMed abstract,[https://www.nature.com/articles/srep07115 CENP-A]which is a centromere-specific histone H3 variant is over expressed in cancer cells and it can be mislocalized ectopically in the form of heterotypic nucleosomes containing H3.3.
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| <scene name='75/752263/Arg_49/1'>ARG 49</scene>
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| </StructureSection>
| | == '''Structural highlights''' == |
| == References == | | |
| 1. Arimura, Y.; Shirayama, K.; Horikoshi, N.; Fujita, R.; Taguchi, H.; Kagawa, W.; Fukagawa, T.; Almouzni, G.; Kurumizaka, H. Crystal structure and stable property of the cancer-associated heterotypic nucleosome containing CENP-A and H3.3. https://www.nature.com/articles/srep07115 (accessed Nov 1, 2020). | | ;Scene #1: Kinesin structure is composed of eight anti-parallel Beta sheets and three alpha helices on opposite sides <scene name='75/752263/Alpha_beta_sheets/5'> Alpha-beta structure </scene> |
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| | ;Scene #2: This is the ATP binding site. Upon the binding of phosphate to ADP, ATP is formed giving Kinesin the energy needed to move the cargo one step a head to its destination <scene name='75/752263/Atp_binding_site/5'> ATP-binding site </scene> |
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| | ;Scene #3: This is the Microtubule-binding site, where Kinesin binds to microtubules for stability <scene name='75/752263/Mt-binding_site/1'> MT-binding site </scene> |
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| 2. Cancer Discovery Science Writers. Histone H3.3 Mutations Are Cancer Type-Specific. https://cancerdiscovery.aacrjournals.org/content/3/12/1329.1 (accessed Nov 14, 2020).
| | ;Scene #4: some patients with CMT show mutation in the p-loop. A missense mutation results in a leucine in place of glutamine affecting signal transmission <scene name='75/752263/Cmt/1'> CMT </scene> |
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| 3. Kallappagoudar, S.; Yadav, R. K.; Lowe, B. R.; Partridge, J. F. Histone H3 mutations--a special role for H3.3 in tumorigenesis? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446520/ (accessed Nov 1, 2020).
| | 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. |
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| 4. UniProt ConsortiumEuropean Bioinformatics InstituteProtein Information ResourceSIB Swiss Institute of Bioinformatics. Histone H3.3. https://www.uniprot.org/uniprot/P84243 (accessed Nov 1, 2020).
| | </StructureSection> |
| | == References == |
| | #file:///C:/Users/Muna/Desktop/Spring%202021/Advanced%20Biochem/pcbi.1003329.pdf |
| | #https://www.ncbi.nlm.nih.gov/books/NBK22572/#:~:text=Kinesins%20moving%20along%20microtubules%20usually,surfaces%20of%20some%20eukaryotic%20cells. |
| | #https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Charcot-Marie-Tooth-Disease-Fact-Sheet |
| | <references/> |