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Potassium channel modulation by a toxin domain in matrix metalloprotease

Rangaraju, Srikant, Khoo, Keith K., Feng, Zhi-Ping, Crossley, George, Nugent, Daniel, Khaytin, Ilya, Chi, Victor, Pham, Cory, Calabresi, Peter, Pennington, Michael W., Norton, RaymondS. and Chandy, K. George 2009, Potassium channel modulation by a toxin domain in matrix metalloprotease, Journal of biological chemistry, vol. 285, no. 12, pp. 9124-9136, doi: 10.1074/jbc.M109.071266.

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Title Potassium channel modulation by a toxin domain in matrix metalloprotease
Author(s) Rangaraju, Srikant
Khoo, Keith K.
Feng, Zhi-Ping
Crossley, George
Nugent, Daniel
Khaytin, Ilya
Chi, Victor
Pham, Cory
Calabresi, Peter
Pennington, Michael W.
Norton, RaymondS.
Chandy, K. George
Journal name Journal of biological chemistry
Volume number 285
Issue number 12
Start page 9124
End page 9136
Total pages 13
Publisher American Society for Biochemistry and Molecular Biology
Place of publication Manchester, Eng.
Publication date 2009
ISSN 1083-351X
Keyword(s) channels/potassium
evolution/protein
membrane/channels
proteases/metalloprotease
toxins
toxin/channels
transport/potassium
Summary 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 (MMP23TxD) that is evolutionarily related to peptide toxins from sea anemones. MMP23TxD 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 MMP23TxD-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.
Notes MARCH
Language eng
DOI 10.1074/jbc.M109.071266
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2009, American Society for Biochemistry and Molecular Biology
Free to Read? Yes
Persistent URL http://hdl.handle.net/10536/DRO/DU:30063787

Document type: Journal Article
Collections: Faculty of Health
School of Medicine
Open Access Collection
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.