4J2J

Crystal structure of AXH domain complex with Capicua

Summary for 4J2J

• Entry DOI: 10.2210/pdb4j2j/pdb
• Related: 4J2L
• Descriptor: Ataxin-1, Protein capicua homolog (3 entities in total)
• Functional Keywords: axh domain, protein-protein interaction, capicua, transcription regulator
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm (By similarity): P54253; Nucleus (Potential): Q96RK0
• Total number of polymer chains: 6
• Total formula weight: 49990.37

Authors

Song, J.-J.,Kim, E. (deposition date: 2013-02-04, release date: 2013-04-03, Last modification date: 2024-11-06)

Primary citation

Kim, E.,Lu, H.-C.,Zoghbi, H.Y.,Song, J.-J.
Structural basis of protein complex formation and reconfiguration by polyglutamine disease protein Ataxin-1 and Capicua
Genes Dev., 27:590-595, 2013

PubMed Abstract: Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by polyglutamine expansion in Ataxin-1 (ATXN1). ATXN1 binds to the transcriptional repressor Capicua (CIC), and the interaction plays a critical role in SCA1 pathogenesis whereby reducing CIC levels rescues SCA1-like phenotypes in a mouse model. The ATXN1/HBP1 (AXH) domain of ATXN1 mediates its homodimerization as well as the interaction with CIC. Here, we present the crystal structure of ATXN1's AXH domain bound to CIC and show that the binding pocket of the AXH domain to CIC overlaps with the homodimerization pocket of the AXH domain. Thus, the binding to CIC disrupts the homodimerization of ATXN1. Furthermore, the binding of CIC reconfigures the complex to allow another form of dimerization mediated by CIC, showing the intricacy of protein complex formation and reconfiguration by ATXN1 and CIC. Identifying the surfaces mediating the interactions between CIC and ATXN1 reveals a critical role for CIC in the reconfiguration of the AXH dimers and might provide insight into ways to target the ATXN1/CIC interactions to modulate SCA1 pathogenesis.

PubMed: 23512657
DOI: 10.1101/gad.212068.112

Experimental method

X-RAY DIFFRACTION (2.5 Å)