2K72
Solution NMR structure of toxin-like potassium channel blocking domain in MMP23
Summary for 2K72
| Entry DOI | 10.2210/pdb2k72/pdb |
| NMR Information | BMRB: 15900 |
| Descriptor | Matrix metalloproteinase-23 (1 entity in total) |
| Functional Keywords | toxin, metalloprotease, mmp23, potassium channel, cleavage on pair of basic residues, glycoprotein, hydrolase, immunoglobulin domain, membrane, metal-binding, signal-anchor, transmembrane, zinc, zymogen |
| Total number of polymer chains | 1 |
| Total formula weight | 4442.34 |
| Authors | Khoo, K.K.,Feng, Z.,Norton, R.S. (deposition date: 2008-07-31, release date: 2010-01-05, Last modification date: 2024-11-06) |
| Primary citation | 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 Cited by 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: 19965868DOI: 10.1074/jbc.M109.071266 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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