Sandbox 7726
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(New page: ==Protein-protein interaction between Ataxin-1 and Capicua== <StructureSection load='4j2l_au' size='340' side='right' caption='Ataxin-1 with Capicua' scene=''> This is a default text for y...) |
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==Protein-protein interaction between Ataxin-1 and Capicua== | ==Protein-protein interaction between Ataxin-1 and Capicua== | ||
<StructureSection load='4j2l_au' size='340' side='right' caption='Ataxin-1 with Capicua' scene=''> | <StructureSection load='4j2l_au' size='340' side='right' caption='Ataxin-1 with Capicua' scene=''> | ||
| - | + | The protein-protein interaction (PPI) between Ataxin-1 (ATXN1) <scene name='78/789347/Atxn1_with_cic/1'>AXH domain and Capicua (CIC)</scene> have been implicated in spinocerebellar ataxia type 1 (SCA1), a neurodegenerative disease primarily caused by polyglutamine expansion in the ATXN1 protein <ref>PMID:23512657</ref>. | |
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== Function == | == Function == | ||
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| + | The binding of CIC to ATXN1 AXH domain leads to the formation and stabilization of ATXN1 oligomers, which are postulated to be the precursors of the disease. | ||
== Disease == | == Disease == | ||
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| + | This disease is primarily caused by the polyglutamine expansion in the ATXN1 protein. However, other factors are also required for the development of SCA1 neuropathology, including phosphorylation of Ser776 and nuclear localization. The synergy between these factors are not yet fully elucidated. | ||
== Relevance == | == Relevance == | ||
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| + | This is a rare neurodegenerative disease, only hitting 1 out 2 out of 100,000 people, and there is no therapeutic agent for this illness yet. | ||
== Structural highlights == | == Structural highlights == | ||
| - | + | Mutation studies of the complex showed that highly conserved residues of CIC, <scene name='78/789347/Cic_impt_residues/2'>W37, L40, and V41</scene> display hydrophobic contacts with highly conserved residues of the AXH domain, <scene name='78/789347/Atxn1_impt_residues/1'>V591, S602, and L686</scene>. These residues were found to be required for the PPI interaction as any combination mutation of these residues lead to the disruption of the PPI formation. | |
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
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<references/> | <references/> | ||
Current revision
Protein-protein interaction between Ataxin-1 and Capicua
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References
- ↑ Kim E, Lu HC, Zoghbi HY, Song JJ. Structural basis of protein complex formation and reconfiguration by polyglutamine disease protein Ataxin-1 and Capicua. Genes Dev. 2013 Mar 15;27(6):590-5. doi: 10.1101/gad.212068.112. PMID:23512657 doi:http://dx.doi.org/10.1101/gad.212068.112
