6JRP

Crystal structure of CIC-HMG-ETV5-DNA complex

6JRP の概要

• エントリーDOI: 10.2210/pdb6jrp/pdb
• 分子名称: Protein capicua homolog, DNA (5'-D(*AP*TP*GP*AP*AP*TP*GP*AP*AP*AP*A)-3'), DNA (5'-D(*TP*TP*TP*TP*CP*AP*TP*TP*CP*AP*T)-3') (3 entities in total)
• 機能のキーワード: repressor, protein-dna complex, transcription
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 66334.29

構造登録者

Song, J.J.,Lee, H. (登録日: 2019-04-05, 公開日: 2019-07-31, 最終更新日: 2024-10-16)

主引用文献

Lee, H.,Song, J.J.
The crystal structure of Capicua HMG-box domain complexed with the ETV5-DNA and its implications for Capicua-mediated cancers.
Febs J., 286:4951-4963, 2019

PubMed Abstract: Capicua (CIC) is a transcriptional repressor and functions downstream of the receptor tyrosine kinase (RTK) signaling pathway. Somatic mutations found in the HMG-box DNA binding domain in CIC have been implicated in several cancers such as oligodendroglioma, oligoastrocytoma, and adenocarcinoma. However, the molecular basis of the DNA binding of CIC and the effect of the somatic mutations found in cancers on DNA binding have not been investigated. Here, we report the crystal structure of the HMG-box domain of CIC complexed with its target DNA, the promoter of Ets Translocation Variant 5 (ETV5). The structure shows that the HMG-box domain has an L-shaped structure and recognizes the minor groove leading to DNA bending. Our structure combined with an electrophoretic mobility shift assay (EMSA) revealed that cancer-associated mutations in the HMG-box domain abrogate the interaction with DNA. These results provide the molecular insight into the DNA binding of CIC and reveal the effects of carcinogenic mutations on DNA binding.

PubMed: 31323153
DOI: 10.1111/febs.15008

実験手法

X-RAY DIFFRACTION (3 Å)