The Penetration Depth for Hanatoxin Partitioning into the Membrane Hydrocarbon Core Measured with Neutron Reflectivity

Hanatoxin (HaTx) from spider venom works as an inhibitor of Kv2.1 channels, most likely by interacting with the voltage sensor (VS). However, the way in which this water-soluble peptide modifies the gating remains poorly understood as the VS is deeply embedded within the bilayer, although it would c...

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Veröffentlicht in:Langmuir : the ACS journal of surfaces and colloids. - 1985. - 34(2018), 30 vom: 31. Juli, Seite 9036-9046
1. Verfasser: Hsieh, Meng-Hsuan (VerfasserIn)
Weitere Verfasser: Huang, Po-Tsang, Liou, Horng-Huei, Liang, Po-Huang, Chen, Pei-Ming, Holt, Stephen A, Yu, Isaac Furay, James, Michael, Shiau, Yu-Shuan, Lee, Ming-Tao, Lin, Tsang-Lang, Lou, Kuo-Long
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2018
Zugriff auf das übergeordnete Werk:Langmuir : the ACS journal of surfaces and colloids
Schlagworte:Journal Article Research Support, Non-U.S. Gov't
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520 |a Hanatoxin (HaTx) from spider venom works as an inhibitor of Kv2.1 channels, most likely by interacting with the voltage sensor (VS). However, the way in which this water-soluble peptide modifies the gating remains poorly understood as the VS is deeply embedded within the bilayer, although it would change its position depending on the membrane potential. To determine whether HaTx can indeed bind to the VS, the depth at which HaTx penetrates into the POPC membranes was measured with neutron reflectivity. Our results successfully demonstrate that HaTx penetrates into the membrane hydrocarbon core (∼9 Å from the membrane surface), not lying on the membrane-water interface as reported for another voltage sensor toxin (VSTx). This difference in penetration depth suggests that the two toxins fix the voltage sensors at different positions with respect to the membrane normal, thereby explaining their different inhibitory effects on the channels. In particular, results from MD simulations constrained by our penetration data clearly demonstrate an appropriate orientation for HaTx to interact with the membranes, which is in line with the biochemical information derived from stopped-flow analysis through delineation of the toxin-VS binding interface 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
700 1 |a Huang, Po-Tsang  |e verfasserin  |4 aut 
700 1 |a Liou, Horng-Huei  |e verfasserin  |4 aut 
700 1 |a Liang, Po-Huang  |e verfasserin  |4 aut 
700 1 |a Chen, Pei-Ming  |e verfasserin  |4 aut 
700 1 |a Holt, Stephen A  |e verfasserin  |4 aut 
700 1 |a Yu, Isaac Furay  |e verfasserin  |4 aut 
700 1 |a James, Michael  |e verfasserin  |4 aut 
700 1 |a Shiau, Yu-Shuan  |e verfasserin  |4 aut 
700 1 |a Lee, Ming-Tao  |e verfasserin  |4 aut 
700 1 |a Lin, Tsang-Lang  |e verfasserin  |4 aut 
700 1 |a Lou, Kuo-Long  |e verfasserin  |4 aut 
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