2K72

Solution NMR structure of toxin-like potassium channel blocking domain in MMP23

2K72 の概要

• エントリーDOI: 10.2210/pdb2k72/pdb
• NMR情報: BMRB: 15900
• 分子名称: Matrix metalloproteinase-23 (1 entity in total)
• 機能のキーワード: toxin, metalloprotease, mmp23, potassium channel, cleavage on pair of basic residues, glycoprotein, hydrolase, immunoglobulin domain, membrane, metal-binding, signal-anchor, transmembrane, zinc, zymogen
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4442.34

構造登録者

Khoo, K.K.,Feng, Z.,Norton, R.S. (登録日: 2008-07-31, 公開日: 2010-01-05, 最終更新日: 2024-11-06)

主引用文献

Rangaraju, S.,Khoo, K.K.,Feng, Z.P.,Crossley, G.,Nugent, D.,Khaytin, I.,Chi, V.,Pham, C.,Calabresi, P.,Pennington, M.W.,Norton, R.S.,Chandy, K.G.
Potassium channel modulation by a toxin domain in matrix metalloprotease 23.
J.Biol.Chem., 285:9124-9136, 2010

PubMed Abstract: Peptide toxins found in a wide array of venoms block K(+) channels, causing profound physiological and pathological effects. Here we describe the first functional K(+) channel-blocking toxin domain in a mammalian protein. MMP23 (matrix metalloprotease 23) contains a domain (MMP23(TxD)) that is evolutionarily related to peptide toxins from sea anemones. MMP23(TxD) shows close structural similarity to the sea anemone toxins BgK and ShK. Moreover, this domain blocks K(+) channels in the nanomolar to low micromolar range (Kv1.6 > Kv1.3 > Kv1.1 = Kv3.2 > Kv1.4, in decreasing order of potency) while sparing other K(+) channels (Kv1.2, Kv1.5, Kv1.7, and KCa3.1). Full-length MMP23 suppresses K(+) channels by co-localizing with and trapping MMP23(TxD)-sensitive channels in the ER. Our results provide clues to the structure and function of the vast family of proteins that contain domains related to sea anemone toxins. Evolutionary pressure to maintain a channel-modulatory function may contribute to the conservation of this domain throughout the plant and animal kingdoms.

PubMed: 19965868
DOI: 10.1074/jbc.M109.071266

実験手法

SOLUTION NMR