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==<scene name='86/868190/Surface_representation/1'>5CZX</scene>==
==<scene name='86/868190/Surface_representation/1'>5CZX</scene>==
<StructureSection load='5czx' size='360' side='right' caption='Crystal structure of Notch3 NRR' scene='86/868190/Surface_representation/1'>
<StructureSection load='5czx' size='360' side='right' caption='Crystal structure of Notch3 NRR' scene='86/868190/Surface_representation/1'>
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<scene name='86/868190/Surface_representation/1'>5CZX</scene> is the <scene name='86/868190/Nrr_domain_alonecentre/2'>NRR (negative regulatory region)</scene> of the [https://www.uniprot.org/uniprot/Q9UM47 neurogenic locus notch homolog protein 3] encoded by the [https://en.wikipedia.org/wiki/Notch_3 NOTCH3 gene]. It's composed of <scene name='86/868190/Lnr_domains/1'>three LIN12/Notch repeats and linker</scene> (LNRs respectively <scene name='86/868190/Lna_domain/1'>LNR-A</scene>,<scene name='86/868190/Lnb_domain/1'>LNR-B</scene>, <scene name='86/868190/Lrn_linker_bc/1'>LNR-B/C linker</scene> and <scene name='86/868190/Lnc/1'>LNR-C</scene> ) and a <scene name='86/868190/Hd/1'>heterodimerization domain (HD)</scene> composed by <scene name='86/868190/Hd-c/1'>HD-C</scene> and <scene name='86/868190/Hd-n/1'>HD-N</scene>.<ref name="oncogene">Bernasconi-Elias, P., Hu, T., Jenkins, D. et al. Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies. Oncogene 35, 6077–6086 (2016). https://doi.org/10.1038/onc.2016.133</ref>.
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== Structural highlights ==
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<scene name='86/868190/Surface_representation/1'>5CZX</scene> is the <scene name='86/868190/Nrr_domain_alonecentre/2'>NRR (negative regulatory region)</scene> of the [https://www.uniprot.org/uniprot/Q9UM47 neurogenic locus notch homolog protein 3] encoded by the [https://en.wikipedia.org/wiki/Notch_3 NOTCH3 gene]. It's composed of <scene name='86/868190/Lnr_domains/1'>three LIN12/Notch repeats and linker</scene> (LNRs respectively <scene name='86/868190/Lna_domain/1'>LNR-A</scene>,<scene name='86/868190/Lnb_domain/1'>LNR-B</scene>, <scene name='86/868190/Lrn_linker_bc/1'>LNR-B/C linker</scene> and <scene name='86/868190/Lnc/1'>LNR-C</scene> ) and a <scene name='86/868190/Hd/1'>heterodimerization domain (HD)</scene> composed by <scene name='86/868190/Hd-c/1'>HD-C</scene> and <scene name='86/868190/Hd-n/1'>HD-N</scene>.<ref name="oncogene">Bernasconi-Elias, P., Hu, T., Jenkins, D. et al. Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies. Oncogene 35, 6077–6086 (2016). https://doi.org/10.1038/onc.2016.133</ref>. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocaids OCA]. For a guided tour on the structure components in complexe with 20358 FAB use [https://proteopedia.org/wiki/fgij/fg.htm?mol=5CZX FirstGlance].
== Function ==
== Function ==
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The ''Notch'' signaling pathway has been studied comprehensively and various aspects of this pathway are very well known. Despite this, it is essential to study the pathway further, so as to understand the role it plays in cancer development and explore novel treatment strategies focusing on the ''Notch'' pathway.
The ''Notch'' signaling pathway has been studied comprehensively and various aspects of this pathway are very well known. Despite this, it is essential to study the pathway further, so as to understand the role it plays in cancer development and explore novel treatment strategies focusing on the ''Notch'' pathway.
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== Structural highlights ==
 
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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.
 

Revision as of 19:58, 19 January 2021

Template:5CZX

Crystal structure of Notch3 NRR

Drag the structure with the mouse to rotate

References

  1. 1.0 1.1 1.2 1.3 Bernasconi-Elias, P., Hu, T., Jenkins, D. et al. Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies. Oncogene 35, 6077–6086 (2016). https://doi.org/10.1038/onc.2016.133
  2. Guo Z, Ohlstein B. Stem cell regulation. Bidirectional Notch signaling regulates Drosophila intestinal stem cell multipotency. Science. 2015 Nov 20;350(6263). pii: 350/6263/aab0988. doi:, 10.1126/science.aab0988. PMID:26586765 doi:http://dx.doi.org/10.1126/science.aab0988
  3. Callahan R, Smith GH. MMTV-induced mammary tumorigenesis: gene discovery, progression to malignancy and cellular pathways. Oncogene. 2000 Feb 21;19(8):992-1001. doi: 10.1038/sj.onc.1203276. PMID:10713682 doi:http://dx.doi.org/10.1038/sj.onc.1203276
  4. Aburjania Z, Jang S, Whitt J, Jaskula-Stzul R, Chen H, Rose JB. The Role of Notch3 in Cancer. Oncologist. 2018 Aug;23(8):900-911. doi: 10.1634/theoncologist.2017-0677. Epub, 2018 Apr 5. PMID:29622701 doi:http://dx.doi.org/10.1634/theoncologist.2017-0677
  5. 5.0 5.1 Aster JC, Pear WS, Blacklow SC. The Varied Roles of Notch in Cancer. Annu Rev Pathol. 2017 Jan 24;12:245-275. doi:, 10.1146/annurev-pathol-052016-100127. Epub 2016 Dec 5. PMID:27959635 doi:http://dx.doi.org/10.1146/annurev-pathol-052016-100127
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