de Chiara Cesira, Kelly Geoff, Menon Rajesh P, McCormick John, Pastore Annalisa
MRC National Institute for Medical Research, The Ridgeway, London, NW7 1AA, UK.
Biomol NMR Assign. 2014 Oct;8(2):325-7. doi: 10.1007/s12104-013-9509-z. Epub 2013 Jul 14.
Ataxin-1 is the protein responsible for the genetically-inherited neurodegenerative disease spinocerebellar ataxia type-1 linked to the expansion of a polyglutamine tract within the protein sequence. The AXH domain of ataxin-1 is essential for the protein to function as a transcriptional co-repressor and mediates the majority of the interactions of ataxin-1 with cellular partners, mainly transcriptional regulators. One of the best characterized ataxin-1 functional partners is Capicua (CIC), a transcriptional repressor involved in signalling pathways that regulate mammalian development, tumorigenesis and, through the interaction with ataxin-1, also neurodegeneration. Complex formation of ataxin-1 with CIC is important both for the function of the wild-type protein and for pathogenesis as transcriptional disregulation is observed since the early stages of the development of the disease. Here we report the (1)H, (13)C and (15)N backbone and side-chain chemical shift assignments of the human ataxin-1 AXH domain in complex with a CIC ligand-peptide.
ataxin-1是一种蛋白质，它与蛋白质序列中多聚谷氨酰胺序列的扩增有关，是导致遗传性神经退行性疾病1型脊髓小脑共济失调的原因。ataxin-1的AXH结构域对于该蛋白质作为转录共抑制因子发挥功能至关重要，并介导了ataxin-1与细胞伙伴（主要是转录调节因子）的大部分相互作用。ataxin-1最具特征的功能伙伴之一是Capicua（CIC），它是一种转录抑制因子，参与调节哺乳动物发育、肿瘤发生的信号通路，并且通过与ataxin-1相互作用，还参与神经退行性变。ataxin-1与CIC形成复合物对于野生型蛋白质的功能以及发病机制都很重要，因为在疾病发展的早期阶段就观察到了转录失调。在此，我们报告了与CIC配体肽形成复合物的人ataxin-1 AXH结构域的（1）H、（13）C和（15）N主链及侧链化学位移归属。
