2MDC

Solution structure of the WW domain of HYPB

2MDC の概要

• エントリーDOI: 10.2210/pdb2mdc/pdb
• 関連するPDBエントリー: 2MDI
• NMR情報: BMRB: 19483
• 分子名称: Histone-lysine N-methyltransferase SETD2 (1 entity in total)
• 機能のキーワード: ww domain, hypb, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus (Probable): Q9BYW2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 5535.12

構造登録者

Gao, Y.G. (登録日: 2013-09-10, 公開日: 2014-09-10, 最終更新日: 2024-05-15)

主引用文献

Gao, Y.G.,Yang, H.,Zhao, J.,Jiang, Y.J.,Hu, H.Y.
Autoinhibitory structure of the WW domain of HYPB/SETD2 regulates its interaction with the proline-rich region of huntingtin
Structure, 22:378-386, 2014

PubMed Abstract: Huntington's disease (HD) is an autosomally dominant neurodegenerative disorder caused by expansion of polyglutamine (polyQ) in the huntingtin (Htt) protein. Htt yeast two-hybrid protein B (HYPB/SETD2), a histone methyltransferase, directly interacts with Htt and is involved in HD pathology. Using NMR techniques, we characterized a polyproline (polyP) stretch at the C terminus of HYPB, which directly interacts with the following WW domain and leads this domain predominantly to be in a closed conformational state. The solution structure shows that the polyP stretch extends from the back and binds to the WW core domain in a typical binding mode. This autoinhibitory structure regulates interaction between the WW domain of HYPB and the proline-rich region (PRR) of Htt, as evidenced by NMR and immunofluorescence techniques. This work provides structural and mechanistic insights into the intramolecular regulation of the WW domain in Htt-interacting partners and will be helpful for understanding the pathology of HD.

PubMed: 24412394
DOI: 10.1016/j.str.2013.12.005

実験手法

SOLUTION NMR