Structural basis of protein complex formation and reconfiguration by polyglutamine disease protein ataxin-1 and Capicua

41Citations
Citations of this article
77Readers
Mendeley users who have this article in their library.

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. © 2013 by Cold Spring Harbor Laboratory Press.

Author supplied keywords

Cite

CITATION STYLE

APA

Kim, E., Lu, H. C., Zoghbi, H. Y., & Song, J. J. (2013). Structural basis of protein complex formation and reconfiguration by polyglutamine disease protein ataxin-1 and Capicua. Genes and Development, 27(6), 590–595. https://doi.org/10.1101/gad.212068.112

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free