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Your search keyword '"Clausen, Michael"' showing total 2 results
Start Over Author "Clausen, Michael" Publisher american association for the advancement of science
2 results on '"Clausen, Michael"'

1. K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac.

Author

Yin Yao Dong, Pike, Ashley C. W., Mackenzie, Alexandra, McClenaghan, Conor, Aryal, Prafulla, Dong, Liang, Quigley, Andrew, Grieben, Mariana, Goubin, Solenne, Mukhopadhyay, Shubhashish, Ruda, Gian Filippo, Clausen, Michael V., Lishuang Cao, Brennan, Paul E., Burgess-Brown, Nicola A., Sansom, Mark S. P., Tucker, Stephen J., and Carpenter, Elisabeth P.

Subjects
*FLUOXETINE, *POTASSIUM channels, *CRYSTAL structure, *ARACHIDONIC acid, *SEROTONIN uptake inhibitors, *POTASSIUM channels regulation
Abstract

TREK-2 (KCNK10/K2P10), a two-pore domain potassium (K2P) channel, is gated by multiple stimuli such as stretch, fatty acids, and pH and by several drugs. However, the mechanisms that control channel gating are unclear. Here we present crystal structures of the human TREK-2 channel (up to 3.4 angstrom resolution) in two conformations and in complex with norfluoxetine, the active metabolite of fluoxetine (Prozac) and a state-dependent blocker of TREK channels. Norfluoxetine binds within intramembrane fenestrations found in only one of these two conformations. Channel activation by arachidonic acid and mechanical stretch involves conversion between these states through movement of the pore-lining helices. These results provide an explanation for TREK channel mechanosensitivity, regulation by diverse stimuli, and possible off-target effects of the serotonin reuptake inhibitor Prozac. [ABSTRACT FROM AUTHOR]

Published
2015
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2. K2P channel gating mechanisms revealed by structures of TREK-2 and a complex with Prozac.

Author

Dong YY, Pike AC, Mackenzie A, McClenaghan C, Aryal P, Dong L, Quigley A, Grieben M, Goubin S, Mukhopadhyay S, Ruda GF, Clausen MV, Cao L, Brennan PE, Burgess-Brown NA, Sansom MS, Tucker SJ, and Carpenter EP

Subjects
Amino Acid Sequence, Arachidonic Acid pharmacology, Binding Sites, Crystallography, X-Ray, Fluoxetine analogs & derivatives, Fluoxetine chemistry, Fluoxetine metabolism, Fluoxetine pharmacology, Humans, Models, Molecular, Molecular Dynamics Simulation, Molecular Sequence Data, Potassium metabolism, Potassium Channels, Tandem Pore Domain antagonists & inhibitors, Potassium Channels, Tandem Pore Domain metabolism, Protein Conformation, Protein Folding, Protein Structure, Secondary, Protein Structure, Tertiary, Ion Channel Gating, Potassium Channels, Tandem Pore Domain chemistry
Abstract

TREK-2 (KCNK10/K2P10), a two-pore domain potassium (K2P) channel, is gated by multiple stimuli such as stretch, fatty acids, and pH and by several drugs. However, the mechanisms that control channel gating are unclear. Here we present crystal structures of the human TREK-2 channel (up to 3.4 angstrom resolution) in two conformations and in complex with norfluoxetine, the active metabolite of fluoxetine (Prozac) and a state-dependent blocker of TREK channels. Norfluoxetine binds within intramembrane fenestrations found in only one of these two conformations. Channel activation by arachidonic acid and mechanical stretch involves conversion between these states through movement of the pore-lining helices. These results provide an explanation for TREK channel mechanosensitivity, regulation by diverse stimuli, and possible off-target effects of the serotonin reuptake inhibitor Prozac., (Copyright © 2015, American Association for the Advancement of Science.)

Published
2015
Full Text
View/download PDF

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